JP2022130552A - 標的化核酸ナノ担体を使用して治療用細胞をプログラムするための組成物及び方法 - Google Patents
標的化核酸ナノ担体を使用して治療用細胞をプログラムするための組成物及び方法 Download PDFInfo
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Abstract
Description
1.対象に投与するための造血系由来の選択された細胞集団の調製方法であって、
造血系由来の選択された細胞集団を含む不均一細胞混合物を含む試料を前記対象から採取する工程と;
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンド
を含む合成ナノ担体に前記試料を暴露することにより、前記選択された細胞集団に前記ナノ担体を選択的に送達し、前記選択された細胞集団内の細胞を改変する工程と;
前記試料内の細胞を拡大培養する工程とを含み;
それにより、前記選択された細胞集団を前記対象に投与できるように調製する、前記方法。
2.前記試料内の前記拡大培養した細胞が、前記選択された細胞集団の改変細胞を含む、実施形態1に記載の方法。
3.更に、前記調製後の選択された細胞集団を細胞組成物に製剤化する工程を含む、実施形態1又は2に記載の方法。
4.更に、前記細胞組成物を前記対象に投与する工程を含む、実施形態3に記載の方法。
5.前記暴露工程の前に、前記不均一細胞混合物における前記選択された細胞集団の百分率を増加させるための単離処置を、全く行わないか又は限定的にしか行わない、実施形態1~4のいずれか一項に記載の方法。
6.前記合成核酸が、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、megaTAL及び/又はジンクフィンガーヌクレアーゼから選択される遺伝子編集剤をコードする、実施形態1~5のいずれか一項に記載の方法。
7.前記合成核酸が、配列番号1のmegaTALをコードする、実施形態6に記載の方法。
8.前記遺伝子編集剤が、Shp-1ホスファターゼ、PD1受容体、T細胞受容体(TCR)、CCR5及び/又はCXCR4をコードする内在性遺伝子を破壊する、実施形態1~7のいずれか一項に記載の方法。
9.前記遺伝子編集剤が、TCRα鎖をコードする内在性遺伝子を破壊する、実施形態1~8のいずれか一項に記載の方法。
10.前記合成核酸が、転写因子、キナーゼ及び/又は細胞表面受容体から選択される、表現型を変化させるタンパク質をコードする、実施形態1~9のいずれか一項に記載の方法。
11.前記表現型を変化させるタンパク質が、FOXO1、LKB1、TCF7、EOMES、ID2、TERT、CCR2b及び/又はCCR4から選択される、実施形態10に記載の方法。
12.前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合する、実施形態1~11のいずれか一項に記載の方法。
13.前記不均一細胞集団がエクソビボ細胞培養物である、実施形態12に記載の方法。
14.前記不均一細胞集団がインビボである、実施形態12に記載の方法。
15.前記選択された細胞ターゲティングリガンドが、T細胞、NK細胞、単球、マクロファージ、樹状細胞、B細胞、造血幹細胞又はそれらの組合せと選択的に結合する、実施形態1~14のいずれか一項に記載の方法。
16.前記選択された細胞ターゲティングリガンドが、リンパ球受容体リガンド、リンパ球受容体抗体、リンパ球受容体ペプチドアプタマー、リンパ球受容体核酸アプタマー、リンパ球受容体スピエゲルマー又はそれらの組合せから選択される結合ドメインを含む、実施形態1~15のいずれか一項に記載の方法。
17.前記選択された細胞ターゲティングリガンドが、T細胞受容体モチーフ、T細胞α鎖、T細胞β鎖、T細胞γ鎖、T細胞δ鎖、CCR7、CD1a、CD1b、CD1c、CD1d、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD39、CD40、CD45RA、CD45RO、CD46、CD52、CD56、CD62L、CD68、CD69、CD80、CD86、CD95、CD101、CD117、CD127、CD133、CD137(4-1BB)、CD148、CD163、CD209、DEC-205、F4/80、IL-4Rα、Sca-1、CTLA-4、GITR、GARP、LAP、グランザイムB、LFA-1又はトランスフェリン受容体と選択的に結合する、実施形態1~16のいずれか一項に記載の方法。
18.前記選択された細胞ターゲティングリガンドが、CD1a、CD1b、CD1c、CD1d、CCR7、CD3、CD4、CD5、CD8、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD35、CD40、CD45RA、CD45RO、CD46、CD52、CD69、CD62L、CD80、CD95、CD127、CD137、CD209又はDEC-205と選択的に結合する、実施形態1~17のいずれか一項に記載の方法。
19.前記選択された細胞ターゲティングリガンドが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体から選択される結合ドメインを含む、実施形態1~18のいずれか一項に記載の方法。
20.前記結合ドメインが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体のscFv断片から構成されるか又はこれらのscFv断片から本質的に構成される、実施形態1~19のいずれか一項に記載の方法。
21.前記合成核酸が合成mRNAである、実施形態1~20のいずれか一項に記載の方法。
22.前記担体が、正電荷をもつ脂質又はポリマーを含む、実施形態1~21のいずれか一項に記載の方法。
23.前記正電荷をもつポリマーが、ポリ(β-アミノエステル)、ポリ(L-リジン)、ポリ(エチレンイミン)(PEI)、ポリ(アミドアミン)デンドリマー(PAMAM)、アミン・エステル共重合体、ポリ(メタクリル酸ジメチルアミノエチル)(PDMAEMA)、キトサン、L-ラクチド・L-リジン共重合体、ポリ[α-(4-アミノブチル)-L-グリコール酸](PAGA)又はポリ(4-ヒドロキシ-L-プロリンエステル)(PHP)を含む、実施形態22に記載の方法。
24.前記コーティングが、中性又は負電荷をもつ脂質又はポリマーを含む、実施形態1~23のいずれか一項に記載の方法。
25.前記中性又は負電荷をもつコーティングが、ポリグルタミン酸(PGA)、ポリ(アクリル酸)、アルギン酸又はコレステリルヘミサクシネート/1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミンを含む、実施形態24に記載の方法。
26.前記中性又は負電荷をもつコーティングが双性イオン型ポリマーを含む、実施形態24又は25に記載の方法。
27.前記中性又は負電荷をもつコーティングがリポソームを含む、実施形態24~26のいずれか一項に記載の方法。
28.前記リポソームが、1,2-ジオレオイル-3-トリメチルアンモニウムプロパン(DOTAP)、1,2-ジ-O-オクタデセニル-3-トリメチルアンモニウムプロパン(DOTMA)、3β-[N-(N’,N’-ジメチルアミノエタン)-カルバモイル]コレステロール(DC-Chol)、ジオクタデシルアミドグリシルスペルミン(DOGS)、コレステロール、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)又は1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)を含む、実施形態27に記載の方法。
29.前記選択された細胞ターゲティングリガンドが、CD4及び/又はCD8と選択的に結合する、実施形態1~28のいずれか一項に記載の方法。
30.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含む、実施形態1~29のいずれか一項に記載の方法。
31.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体のscFv断片から選択される結合ドメインを含む、実施形態1~30のいずれか一項に記載の方法。
32.前記担体がポリ(β-アミノエステル)を含む、実施形態1~31のいずれか一項に記載の方法。
33.前記コーティングがポリグルタミン酸(PGA)を含む、実施形態1~32のいずれか一項に記載の方法。
34.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含み、前記担体がポリ(β-アミノエステル)を含み、前記コーティングがポリグルタミン酸(PGA)を含む、実施形態1~33のいずれか一項に記載の方法。
35.対象を治療するための細胞の調製方法であって、
対象からリンパ球を採取する工程;及び
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む合成ナノ担体と前記リンパ球を結合させる工程を含み;
前記結合後に前記リンパ球が前記核酸を一過性発現するように前記ナノ担体を前記リンパ球に選択的に取込ませる、前記方法。
36.更に、前記リンパ球を拡大培養する工程を含む、実施形態35に記載の方法。
37.更に、前記リンパ球を細胞組成物に製剤化する工程を含む、実施形態35又は36に記載の方法。
38.前記暴露工程の前に、前記不均一細胞混合物における前記選択された細胞集団の百分率を増加させるための単離処置を全く行わないか又は限定的にしか行わない、実施形態35~37のいずれか一項に記載の方法。
39.前記合成核酸が、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、megaTAL及び/又はジンクフィンガーヌクレアーゼから選択される遺伝子編集剤をコードする、実施形態35~38のいずれか一項に記載の方法。
40.前記合成核酸が、配列番号1のmegaTALをコードする、実施形態35~39のいずれか一項に記載の方法。
41.前記遺伝子編集剤が、Shp-1ホスファターゼ、PD1受容体、T細胞受容体(TCR)、CCR5及び/又はCXCR4をコードする内在性遺伝子を破壊する、実施形態35~40のいずれか一項に記載の方法。
42.前記遺伝子編集剤が、TCRα鎖をコードする内在性遺伝子を破壊する、実施形態35~41のいずれか一項に記載の方法。
43.前記合成核酸が、転写因子、キナーゼ及び/又は細胞表面受容体から選択される、表現型を変化させるタンパク質をコードする、実施形態35~42のいずれか一項に記載の方法。
44.前記表現型を変化させるタンパク質が、FOXO1、LKB1、TCF7、EOMES、ID2、TERT、CCR2b及び/又はCCR4から選択される、実施形態43に記載の方法。
45.前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合する、実施形態35~44のいずれか一項に記載の方法。
46.前記不均一細胞集団が、エクソビボ細胞培養物である、実施形態45に記載の方法。
47.前記不均一細胞集団が、インビボである、実施形態45に記載の方法。
48.前記選択された細胞ターゲティングリガンドが、T細胞、NK細胞、単球、マクロファージ、樹状細胞、B細胞、造血幹細胞又はそれらの組合せと選択的に結合する、実施形態35~47のいずれか一項に記載の方法。
49.前記選択された細胞ターゲティングリガンドが、リンパ球受容体リガンド、リンパ球受容体抗体、リンパ球受容体ペプチドアプタマー、リンパ球受容体核酸アプタマー、リンパ球受容体スピエゲルマー又はそれらの組合せから選択される結合ドメインを含む、実施形態35~48のいずれか一項に記載の方法。
50.前記選択された細胞ターゲティングリガンドが、T細胞受容体モチーフ、T細胞α鎖、T細胞β鎖、T細胞γ鎖、T細胞δ鎖、CCR7、CD1a、CD1b、CD1c、CD1d、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD39、CD40、CD45RA、CD45RO、CD46、CD52、CD56、CD62L、CD68、CD69、CD80、CD86、CD95、CD101、CD117、CD127、CD133、CD137(4-1BB)、CD148、CD163、CD209、DEC-205、F4/80、IL-4Rα、Sca-1、CTLA-4、GITR、GARP、LAP、グランザイムB、LFA-1又はトランスフェリン受容体と選択的に結合する、実施形態35~49のいずれか一項に記載の方法。
51.前記選択された細胞ターゲティングリガンドが、CD1a、CD1b、CD1c、CD1d、CCR7、CD3、CD4、CD5、CD8、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD35、CD40、CD45RA、CD45RO、CD46、CD52、CD62L、CD69、CD80、CD95、CD127、CD137、CD209又はDEC-205と選択的に結合する、実施形態35~50のいずれか一項に記載の方法。
52.前記選択された細胞ターゲティングリガンドが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体から選択される結合ドメインを含む、実施形態35~51のいずれか一項に記載の方法。
53.前記結合ドメインが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体のscFv断片から構成されるか又はこれらのscFv断片から本質的に構成される、実施形態35~52のいずれか一項に記載の方法。
54.前記合成核酸が、合成mRNAである、実施形態35~53のいずれか一項に記載の方法。
55.前記担体が、正電荷をもつ脂質又はポリマーを含む、実施形態35~54のいずれか一項に記載の方法。
56.前記正電荷をもつ脂質又はポリマーが、ポリ(β-アミノエステル)、ポリ(L-リジン)、ポリ(エチレンイミン)(PEI)、ポリ(アミドアミン)デンドリマー(PAMAM)、アミン・エステル共重合体、ポリ(メタクリル酸ジメチルアミノエチル)(PDMAEMA)、キトサン、L-ラクチド・L-リジン共重合体、ポリ[α-(4-アミノブチル)-L-グリコール酸](PAGA)又はポリ(4-ヒドロキシ-L-プロリンエステル)(PHP)を含む、実施形態55に記載の方法。
57.前記コーティングが、中性又は負電荷をもつ脂質又はポリマーを含む、実施形態35~56のいずれか一項に記載の方法。
58.前記中性又は負電荷をもつコーティングが、ポリグルタミン酸(PGA)、ポリ(アクリル酸)、アルギン酸又はコレステリルヘミサクシネート/1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミンを含む、実施形態57に記載の方法。
59.前記中性又は負電荷をもつコーティングが双性イオン型ポリマーを含む、実施形態57又は58に記載の方法。
60.前記中性又は負電荷をもつコーティングが、リポソームを含む、実施形態57~59のいずれか一項に記載の方法。
61.前記リポソームが、1,2-ジオレオイル-3-トリメチルアンモニウムプロパン(DOTAP)、1,2-ジ-O-オクタデセニル-3-トリメチルアンモニウムプロパン(DOTMA)、3β-[N-(N’,N’-ジメチルアミノエタン)-カルバモイル]コレステロール(DC-Chol)、ジオクタデシルアミドグリシルスペルミン(DOGS)、コレステロール、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)又は1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)を含む、実施形態60に記載の方法。
62.前記選択された細胞ターゲティングリガンドが、CD4及び/又はCD8と選択的に結合する、実施形態35~61のいずれか一項に記載の方法。
63.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含む、実施形態35~62のいずれか一項に記載の方法。
64.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体のscFv断片から選択される結合ドメインを含む、実施形態35~63のいずれか一項に記載の方法。
65.前記担体がポリ(β-アミノエステル)を含む、実施形態35~64のいずれか一項に記載の方法。
66.前記コーティングが、ポリグルタミン酸(PGA)を含む、実施形態35~65のいずれか一項に記載の方法。
67.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含み、前記担体がポリ(β-アミノエステル)を含み、前記コーティングがポリグルタミン酸(PGA)を含む、実施形態35~66のいずれか一項に記載の方法。
68.治療を必要とする対象の治療方法であって、
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含むナノ担体により細胞に選択的に送達された前記核酸の一過性発現により改変された前記細胞を治療有効量投与する段階を含み;
前記結合後に前記リンパ球が前記核酸を一過性発現するように前記ナノ担体を前記リンパ球に選択的に取込ませることにより、治療を必要とする前記対象を治療する、前記方法。
69.対象に投与するための選択された細胞集団の調製方法であって、
選択された細胞集団を含む不均一細胞混合物を含む試料を前記対象から採取する工程;
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む合成ナノ担体に前記試料を暴露することにより、前記選択された細胞集団に前記ナノ担体を選択的に送達し、前記選択された細胞集団内の細胞を改変する工程;及び
前記試料内の細胞を拡大培養する工程を含み;
それにより、前記選択された細胞集団を前記対象に投与できるように調製する、前記方法。
70.(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む、合成ナノ担体。
71.前記合成核酸が、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、megaTAL及び/又はジンクフィンガーヌクレアーゼから選択される遺伝子編集剤をコードする、実施形態70に記載の合成ナノ担体。
72.前記合成核酸が、配列番号1のmegaTALをコードする、実施形態70又は71に記載の合成ナノ担体。
73.前記遺伝子編集剤が、Shp-1ホスファターゼ、PD1受容体、T細胞受容体(TCR)、CCR5及び/又はCXCR4をコードする内在性遺伝子を破壊する、実施形態70~72のいずれか一項に記載の合成ナノ担体。
74.前記遺伝子編集剤が、TCRα鎖をコードする内在性遺伝子を破壊する、実施形態70~73のいずれか一項に記載の合成ナノ担体。
75.前記合成核酸が、転写因子、キナーゼ及び/又は細胞表面受容体から選択される、表現型を変化させるタンパク質をコードする、実施形態70~74のいずれか一項に記載の合成ナノ担体。
76.前記表現型を変化させるタンパク質が、FOXO1、LKB1、TCF7、EOMES、ID2、TERT、CCR2b及び/又はCCR4から選択される、実施形態75に記載の合成ナノ担体。
77.前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合する、実施形態70~76のいずれか一項に記載の合成ナノ担体。
78.前記不均一細胞集団が、エクソビボ細胞培養物である、実施形態77に記載の合成ナノ担体。
79.前記不均一細胞集団が、インビボである、実施形態77に記載の合成ナノ担体。
80.前記選択された細胞ターゲティングリガンドが、T細胞、NK細胞、単球、マクロファージ、樹状細胞、B細胞、造血幹細胞又はそれらの組合せと選択的に結合する、実施形態70~79のいずれか一項に記載の合成ナノ担体。
81.前記選択された細胞ターゲティングリガンドが、リンパ球受容体リガンド、リンパ球受容体抗体、リンパ球受容体ペプチドアプタマー、リンパ球受容体核酸アプタマー、リンパ球受容体スピエゲルマー又は又はそれらの組合せから選択される結合ドメインを含む、実施形態70~80のいずれか一項に記載の合成ナノ担体。
82.前記選択された細胞ターゲティングリガンドが、T細胞受容体モチーフ、T細胞α鎖、T細胞β鎖、T細胞γ鎖、T細胞δ鎖、CCR7、CD1a、CD1b、CD1c、CD1d、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD39、CD40、CD45RA、CD45RO、CD46、CD52、CD56、CD62L、CD68、CD69、CD80、CD86、CD95、CD101、CD117、CD127、CD133、CD137(4-1BB)、CD148、CD163、CD209、DEC-205、F4/80、IL-4Rα、Sca-1、CTLA-4、GITR、GARP、LAP、グランザイムB、LFA-1又はトランスフェリン受容体と選択的に結合する、実施形態70~81のいずれか一項に記載の合成ナノ担体。
83.前記選択された細胞ターゲティングリガンドが、CD1a、CD1b、CD1c、CD1d、CCR7、CD3、CD4、CD5、CD8、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD35、CD40、CD45RA、CD45RO、CD46、CD52、CD62L、CD69、CD80、CD95、CD127、CD137、CD209又はDEC-205と選択的に結合する、実施形態70~82のいずれか一項に記載の合成ナノ担体。
84.前記選択された細胞ターゲティングリガンドが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体から選択される結合ドメインを含む、実施形態70~83のいずれか一項に記載の合成ナノ担体。
85.前記結合ドメインが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体のscFv断片から構成されるか又はこれらのscFv断片から本質的に構成される、実施形態70~84のいずれか一項に記載の合成ナノ担体。
86.前記合成核酸が、合成mRNAである、実施形態70~85のいずれか一項に記載の合成ナノ担体。
87.前記担体が、正電荷をもつ脂質又はポリマーを含む、実施形態70~86のいずれか一項に記載の合成ナノ担体。
88.前記正電荷をもつ脂質又はポリマーが、ポリ(β-アミノエステル)、ポリ(L-リジン)、ポリ(エチレンイミン)(PEI)、ポリ(アミドアミン)デンドリマー(PAMAM)、アミン・エステル共重合体、ポリ(メタクリル酸ジメチルアミノエチル)(PDMAEMA)、キトサン、L-ラクチド・L-リジン共重合体、ポリ[α-(4-アミノブチル)-L-グリコール酸](PAGA)又はポリ(4-ヒドロキシ-L-プロリンエステル)(PHP)を含む、実施形態87に記載の合成ナノ担体。
89.前記コーティングが、中性又は負電荷をもつ脂質又はポリマーを含む、実施形態70~88のいずれか一項に記載の合成ナノ担体。
90.前記中性又は負電荷をもつコーティングが、ポリグルタミン酸(PGA)、ポリ(アクリル酸)、アルギン酸又はコレステリルヘミサクシネート/1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミンを含む、実施形態89に記載の合成ナノ担体。
91.前記中性又は負電荷をもつコーティングが、双性イオン型ポリマーを含む、実施形態89又は90に記載の合成ナノ担体。
92.前記中性又は負電荷をもつコーティングが、リポソームを含む、実施形態89~91のいずれか一項に記載の合成ナノ担体。
93.前記リポソームが、1,2-ジオレオイル-3-トリメチルアンモニウムプロパン(DOTAP)、1,2-ジ-O-オクタデセニル-3-トリメチルアンモニウムプロパン(DOTMA)、3β-[N-(N’,N’-ジメチルアミノエタン)-カルバモイル]コレステロール(DC-Chol)、ジオクタデシルアミドグリシルスペルミン(DOGS)、コレステロール、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)又は1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)を含む、実施形態92に記載の合成ナノ担体。
94.前記選択された細胞ターゲティングリガンドが、CD4及び/又はCD8と選択的に結合する、実施形態70~93のいずれか一項に記載の合成ナノ担体。
95.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含む、実施形態70~94のいずれか一項に記載の合成ナノ担体。
96.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体のscFv断片から選択される結合ドメインを含む、実施形態70~95のいずれか一項に記載の合成ナノ担体。
97.前記担体がポリ(β-アミノエステル)を含む、実施形態70~96のいずれか一項に記載の合成ナノ担体。
98.前記コーティングがポリグルタミン酸(PGA)を含む、実施形態70~97のいずれか一項に記載の合成ナノ担体。
99.前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含み、前記担体がポリ(β-アミノエステル)を含み、前記コーティングがポリグルタミン酸(PGA)を含む、実施形態70~98のいずれか一項に記載の合成ナノ担体。
100.実施形態70~99のいずれか一項に記載の合成ナノ担体を含有する、組成物。
101.治療を必要とする対象の治療方法であって、治療有効量の実施形態70~99のいずれか一項に記載の合成ナノ担体又は実施形態100に記載の組成物を投与することにより、治療を必要とする前記対象を治療する、前記方法。
102.CAR又はTCRをコードする核酸を選択された細胞種に選択的に送達するための、本願に開示するナノ担体の使用。
緒言。キメラ抗原受容体(CAR)又はT細胞受容体(TCR)を発現するようにT細胞を遺伝子操作することにより、がんに対する免疫応答を誘導する方法は、大きな成果を挙げ始めている治療法であり、重要な臨床試験が着手されようとしている。T細胞を生物工学的に操作して「リビングドラッグ(living drug:生きた薬剤)」に転化させ、数を増やすことができ、腫瘍細胞を逐次破壊することができ、最終的に寿命の長いメモリーT細胞に分化できるようにする方法では、受容体トランスジーンをリンパ球のゲノムに安定的に組込むことが必要である。ウイルスベクターは、作製に時間と費用がかかり、パッケージングできる遺伝子のサイズと個数が限られているが、用途に合わせた腫瘍認識能をもつようにこれらの細胞をプログラムするために、現時点で最も有効な手段である(Zhang et al.,Nat Commun 6,7639(2015);Cribbs et al.,BMC Biotechnol 13,98(2013))。
Foxo13Aフォワード:GGACAGCCTAGAAAGAGCAG(配列番号55)
Foxo13Aプローブ:AGGTCGGCGTAGCTCAGATTGC(配列番号56)
Foxo13Aリバース:CTCTTGACCATCCACTCGTAG(配列番号57)。
Claims (102)
- 対象に投与するための造血系由来の選択された細胞集団の調製方法であって、
造血系由来の選択された細胞集団を含む不均一細胞混合物を含む試料を前記対象から採取する工程;
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む合成ナノ担体に前記試料を暴露することにより、前記選択された細胞集団に前記ナノ担体を選択的に送達し、前記選択された細胞集団内の細胞を改変する工程;及び
前記試料内の細胞を拡大培養する工程を含み;
それにより、前記選択された細胞集団を前記対象に投与できるように調製する、前記方法。 - 前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合し、受容体誘導性エンドサイトーシスを開始する、請求項1に記載の方法。
- 前記試料内の前記拡大培養した細胞が、前記選択された細胞集団の改変細胞を含む、請求項1に記載の方法。
- 更に、調製後の前記選択された細胞集団を細胞組成物に製剤化する工程を含む、請求項1に記載の方法。
- 更に、前記細胞組成物を前記対象に投与する工程を含む、請求項4に記載の方法。
- 前記暴露工程の前に、前記不均一細胞混合物における前記選択された細胞集団の百分率を増加させるための単離処置を、全く行わないか又は限定的にしか行わない、請求項1に記載の方法。
- 前記合成核酸が、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、megaTAL及び/又はジンクフィンガーヌクレアーゼから選択される遺伝子編集剤をコードする、請求項1に記載の方法。
- 前記合成核酸が、配列番号1のmegaTALをコードする、請求項7に記載の方法。
- 前記遺伝子編集剤が、Shp-1ホスファターゼ、PD1受容体、T細胞受容体(TCR)、CCR5及び/又はCXCR4をコードする内在性遺伝子を破壊する、請求項1に記載の方法。
- 前記遺伝子編集剤が、TCRα鎖をコードする内在性遺伝子を破壊する、請求項1に記載の方法。
- 前記合成核酸が、転写因子、キナーゼ及び/又は細胞表面受容体から選択される表現型を変化させるタンパク質をコードする、請求項1に記載の方法。
- 前記表現型を変化させるタンパク質が、FOXO1、LKB1、TCF7、EOMES、ID2、TERT、CCR2b及び/又はCCR4から選択される、請求項10に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合し、受容体誘導性エンドサイトーシスを開始する、請求項1に記載の方法。
- 前記不均一細胞集団が、エクソビボ細胞培養物である、請求項13に記載の方法。
- 前記不均一細胞集団が、インビボである、請求項13に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、T細胞、NK細胞、単球、マクロファージ、樹状細胞、B細胞、造血幹細胞又はそれらの組合せと選択的に結合する、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、リンパ球受容体リガンド、リンパ球受容体抗体、リンパ球受容体ペプチドアプタマー、リンパ球受容体核酸アプタマー、リンパ球受容体スピエゲルマー又はそれらの組合せから選択される結合ドメインを含む、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、T細胞受容体モチーフ、T細胞α鎖、T細胞β鎖、T細胞γ鎖、T細胞δ鎖、CCR7、CD1a、CD1b、CD1c、CD1d、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD39、CD40、CD45RA、CD45RO、CD46、CD52、CD56、CD62L、CD68、CD69、CD80、CD86、CD95、CD101、CD117、CD127、CD133、CD137(4-1BB)、CD148、CD163、CD209、DEC-205、F4/80、IL-4Rα、Sca-1、CTLA-4、GITR、GARP、LAP、グランザイムB、LFA-1又はトランスフェリン受容体と選択的に結合する、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD1a、CD1b、CD1c、CD1d、CCR7、CD3、CD4、CD5、CD8、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD35、CD40、CD45RA、CD45RO、CD46、CD52、CD69、CD62L、CD80、CD95、CD127、CD137、CD209又はDEC-205と選択的に結合する、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体から選択される結合ドメインを含む、請求項1に記載の方法。
- 前記結合ドメインが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体の、scFv断片から構成されるか又はこれらのscFv断片から本質的に構成される、請求項1に記載の方法。
- 前記合成核酸が、合成mRNAである、請求項1に記載の方法。
- 前記担体が、正電荷をもつ脂質又はポリマーを含む、請求項1に記載の方法。
- 前記正電荷をもつポリマーが、ポリ(β-アミノエステル)、ポリ(L-リジン)、ポリ(エチレンイミン)(PEI)、ポリ(アミドアミン)デンドリマー(PAMAM)、アミン・エステル共重合体、ポリ(メタクリル酸ジメチルアミノエチル)(PDMAEMA)、キトサン、L-ラクチド・L-リジン共重合体、ポリ[α-(4-アミノブチル)-L-グリコール酸](PAGA)又はポリ(4-ヒドロキシ-L-プロリンエステル)(PHP)を含む、請求項22に記載の方法。
- 前記コーティングが、中性又は負電荷をもつ脂質又はポリマーを含む、請求項1に記載の方法。
- 前記中性又は負電荷をもつコーティングが、ポリグルタミン酸(PGA)、ポリ(アクリル酸)、アルギン酸又はコレステリルヘミサクシネート/1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミンを含む、請求項24に記載の方法。
- 前記中性又は負電荷をもつコーティングが、双性イオン型ポリマーを含む、請求項24に記載の方法。
- 前記中性又は負電荷をもつコーティングが、リポソームを含む、請求項24に記載の方法。
- 前記リポソームが、1,2-ジオレオイル-3-トリメチルアンモニウムプロパン(DOTAP)、1,2-ジ-O-オクタデセニル-3-トリメチルアンモニウムプロパン(DOTMA)、3β-[N-(N’,N’-ジメチルアミノエタン)-カルバモイル]コレステロール(DC-Chol)、ジオクタデシルアミドグリシルスペルミン(DOGS)、コレステロール、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)又は1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)を含む、請求項27に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4及び/又はCD8と選択的に結合する、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含む、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体のscFv断片から選択される結合ドメインを含む、請求項1に記載の方法。
- 前記担体が、ポリ(β-アミノエステル)を含む、請求項1に記載の方法。
- 前記コーティングが、ポリグルタミン酸(PGA)を含む、請求項1に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含み、前記担体が、ポリ(β-アミノエステル)を含み、前記コーティングが、ポリグルタミン酸(PGA)を含む、請求項1に記載の方法。
- 対象を治療するための細胞の調製方法であって、
対象からリンパ球を採取する工程;及び
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む合成ナノ担体と前記リンパ球とを結合させる工程を含み;
前記結合後に前記リンパ球が前記核酸を一過性発現するように前記ナノ担体を前記リンパ球に選択的に取込ませる、前記方法。 - 更に、前記リンパ球を拡大培養する工程を含む、請求項35に記載の方法。
- 更に、前記リンパ球を細胞組成物に製剤化する工程を含む、請求項35に記載の方法。
- 前記暴露工程の前に、前記不均一細胞混合物における前記選択された細胞集団の百分率を増加させるための単離処置を、全く行わないか又は限定的にしか行わない、請求項35に記載の方法。
- 前記合成核酸が、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、megaTAL及び/又はジンクフィンガーヌクレアーゼから選択される遺伝子編集剤をコードする、請求項35に記載の方法。
- 前記合成核酸が、配列番号1のmegaTALをコードする、請求項35に記載の方法。
- 前記遺伝子編集剤が、Shp-1ホスファターゼ、PD1受容体、T細胞受容体(TCR)、CCR5及び/又はCXCR4をコードする内在性遺伝子を破壊する、請求項35に記載の方法。
- 前記遺伝子編集剤が、TCRα鎖をコードする内在性遺伝子を破壊する、請求項35に記載の方法。
- 前記合成核酸が、転写因子、キナーゼ及び/又は細胞表面受容体から選択される、表現型を変化させるタンパク質をコードする、請求項35に記載の方法。
- 前記表現型を変化させるタンパク質が、FOXO1、LKB1、TCF7、EOMES、ID2、TERT、CCR2b及び/又はCCR4から選択される、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合する、請求項35に記載の方法。
- 前記不均一細胞集団が、エクソビボ細胞培養物である、請求項45に記載の方法。
- 前記不均一細胞集団が、インビボである、請求項45に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、T細胞、NK細胞、単球、マクロファージ、樹状細胞、B細胞、造血幹細胞又はそれらの組合せと選択的に結合する、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、リンパ球受容体リガンド、リンパ球受容体抗体、リンパ球受容体ペプチドアプタマー、リンパ球受容体核酸アプタマー、リンパ球受容体スピエゲルマー又はそれらの組合せから選択される結合ドメインを含む、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、T細胞受容体モチーフ、T細胞α鎖、T細胞β鎖、T細胞γ鎖、T細胞δ鎖、CCR7、CD1a、CD1b、CD1c、CD1d、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD39、CD40、CD45RA、CD45RO、CD46、CD52、CD56、CD62L、CD68、CD69、CD80、CD86、CD95、CD101、CD117、CD127、CD133、CD137(4-1BB)、CD148、CD163、CD209、DEC-205、F4/80、IL-4Rα、Sca-1、CTLA-4、GITR、GARP、LAP、グランザイムB、LFA-1又はトランスフェリン受容体と選択的に結合する、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD1a、CD1b、CD1c、CD1d、CCR7、CD3、CD4、CD5、CD8、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD35、CD40、CD45RA、CD45RO、CD46、CD52、CD62L、CD69、CD80、CD95、CD127、CD137、CD209又はDEC-205と選択的に結合する、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体から選択される結合ドメインを含む、請求項35に記載の方法。
- 前記結合ドメインが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体のscFv断片から構成されるか、又はこれらのscFv断片から本質的に構成される、請求項35に記載の方法。
- 前記合成核酸が、合成mRNAである、請求項35に記載の方法。
- 前記担体が、正電荷をもつ脂質又はポリマーを含む、請求項35に記載の方法。
- 前記正電荷をもつ脂質又はポリマーが、ポリ(β-アミノエステル)、ポリ(L-リジン)、ポリ(エチレンイミン)(PEI)、ポリ(アミドアミン)デンドリマー(PAMAM)、アミン・エステル共重合体、ポリ(メタクリル酸ジメチルアミノエチル)(PDMAEMA)、キトサン、L-ラクチド・L-リジン共重合体、ポリ[α-(4-アミノブチル)-L-グリコール酸](PAGA)又はポリ(4-ヒドロキシ-L-プロリンエステル)(PHP)を含む、請求項55に記載の方法。
- 前記コーティングが、中性又は負電荷をもつ脂質又はポリマーを含む、請求項55に記載の方法。
- 前記中性又は負電荷をもつコーティングが、ポリグルタミン酸(PGA)、ポリ(アクリル酸)、アルギン酸又はコレステリルヘミサクシネート/1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミンを含む、請求項57に記載の方法。
- 前記中性又は負電荷をもつコーティングが、双性イオン型ポリマーを含む、請求項57に記載の方法。
- 前記中性又は負電荷をもつコーティングが、リポソームを含む、請求項57に記載の方法。
- 前記リポソームが、1,2-ジオレオイル-3-トリメチルアンモニウムプロパン(DOTAP)、1,2-ジ-O-オクタデセニル-3-トリメチルアンモニウムプロパン(DOTMA)、3β-[N-(N’,N’-ジメチルアミノエタン)-カルバモイル]コレステロール(DC-Chol)、ジオクタデシルアミドグリシルスペルミン(DOGS)、コレステロール、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)又は1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)を含む、請求項60に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4及び/又はCD8と選択的に結合する、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含む、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体のscFv断片から選択される結合ドメインを含む、請求項35に記載の方法。
- 前記担体が、ポリ(β-アミノエステル)を含む、請求項35に記載の方法。
- 前記コーティングが、ポリグルタミン酸(PGA)を含む、請求項35に記載の方法。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含み、前記担体が、ポリ(β-アミノエステル)を含み、前記コーティングが、ポリグルタミン酸(PGA)を含む、請求項35に記載の方法。
- 治療を必要とする対象の治療方法であって、
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含むナノ担体により細胞に選択的に送達された前記核酸の一過性発現により改変された前記細胞を、治療有効量投与する段階を含み;
前記結合後に前記リンパ球が前記核酸を一過性発現するように前記ナノ担体を前記リンパ球に選択的に取込ませることにより、治療を必要とする前記対象を治療する、前記方法。 - 対象に投与するための選択された細胞集団の調製方法であって、
選択された細胞集団を含む不均一細胞混合物を含む試料を前記対象から採取する工程;
(i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする合成核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む合成ナノ担体に前記試料を暴露することにより、前記選択された細胞集団に前記ナノ担体を選択的に送達し、前記選択された細胞集団内の細胞を改変する工程;及び
前記試料内の細胞を拡大培養する工程を含み;
それにより、前記選択された細胞集団の前記対象への投与のために調製する、前記方法。 - (i)正電荷をもつ担体の内側に封入されており、遺伝子編集剤又は表現型を変化させるタンパク質をコードする核酸と;
(ii)前記担体の外表面に設けられた中性又は負電荷をもつコーティングと;
(iii)前記コーティングの表面から突き出した選択された細胞ターゲティングリガンドと
を含む合成ナノ担体。 - 前記合成核酸が、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、megaTAL及び/又はジンクフィンガーヌクレアーゼから選択される遺伝子編集剤をコードする、請求項70に記載の合成ナノ担体。
- 前記合成核酸が、配列番号1のmegaTALをコードする、請求項70に記載の合成ナノ担体。
- 前記遺伝子編集剤が、Shp-1ホスファターゼ、PD1受容体、T細胞受容体(TCR)、CCR5及び/又はCXCR4をコードする内在性遺伝子を破壊する、請求項70に記載の合成ナノ担体。
- 前記遺伝子編集剤が、TCRα鎖をコードする内在性遺伝子を破壊する、請求項70に記載の合成ナノ担体。
- 前記合成核酸が、転写因子、キナーゼ及び/又は細胞表面受容体から選択される、表現型を変化させるタンパク質をコードする、請求項70に記載の合成ナノ担体。
- 前記表現型を変化させるタンパク質が、FOXO1、LKB1、TCF7、EOMES、ID2、TERT、CCR2b及び/又はCCR4から選択される、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、不均一細胞集団内のリンパ球と選択的に結合する、請求項70に記載の合成ナノ担体。
- 前記不均一細胞集団が、エクソビボ細胞培養物である、請求項77に記載の合成ナノ担体。
- 前記不均一細胞集団が、インビボである、請求項77に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、T細胞、NK細胞、単球、マクロファージ、樹状細胞、B細胞、造血幹細胞又はそれらの組合せと選択的に結合する、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、リンパ球受容体リガンド、リンパ球受容体抗体、リンパ球受容体ペプチドアプタマー、リンパ球受容体核酸アプタマー、リンパ球受容体スピエゲルマー又はそれらの組合せから選択される結合ドメインを含む、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、T細胞受容体モチーフ、T細胞α鎖、T細胞β鎖、T細胞γ鎖、T細胞δ鎖、CCR7、CD1a、CD1b、CD1c、CD1d、CD3、CD4、CD5、CD7、CD8、CD11b、CD11c、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD34、CD35、CD39、CD40、CD45RA、CD45RO、CD46、CD52、CD56、CD62L、CD68、CD69、CD80、CD86、CD95、CD101、CD117、CD127、CD133、CD137(4-1BB)、CD148、CD163、CD209、DEC-205、F4/80、IL-4Rα、Sca-1、CTLA-4、GITR、GARP、LAP、グランザイムB、LFA-1又はトランスフェリン受容体と選択的に結合する、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、CD1a、CD1b、CD1c、CD1d、CCR7、CD3、CD4、CD5、CD8、CD16、CD19、CD20、CD21、CD22、CD25、CD28、CD35、CD40、CD45RA、CD45RO、CD46、CD52、CD62L、CD69、CD80、CD95、CD127、CD137、CD209又はDEC-205と選択的に結合する、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体から選択される結合ドメインを含む、請求項70に記載の合成ナノ担体。
- 前記結合ドメインが、T細胞α鎖抗体、T細胞β鎖抗体、T細胞γ鎖抗体、T細胞δ鎖抗体、CCR7抗体、CD1a抗体、CD1b抗体、CD1c抗体、CD1d抗体、CD3抗体、CD4抗体、CD5抗体、CD7抗体、CD8抗体、CD11b抗体、CD11c抗体、CD16抗体、CD19抗体、CD20抗体、CD21抗体、CD22抗体、CD25抗体、CD28抗体、CD34抗体、CD35抗体、CD39抗体、CD40抗体、CD45RA抗体、CD45RO抗体、CD46抗体、CD52抗体、CD56抗体、CD62L抗体、CD68抗体、CD69抗体、CD80抗体、CD86抗体、CD95抗体、CD101抗体、CD117抗体、CD127抗体、CD133抗体、CD137(4-1BB)抗体、CD148抗体、CD163抗体、CD209抗体、DEC-205抗体、F4/80抗体、IL-4Rα抗体、Sca-1抗体、CTLA-4抗体、GITR抗体、GARP抗体、LAP抗体、グランザイムB抗体、LFA-1抗体又はトランスフェリン受容体抗体のscFv断片から構成されるか、又はそれらのscFv断片から本質的に構成される、請求項70に記載の合成ナノ担体。
- 前記合成核酸が、合成mRNAである、請求項70に記載の合成ナノ担体。
- 前記担体が、正電荷をもつ脂質又はポリマーを含む、請求項70に記載の合成ナノ担体。
- 前記正電荷をもつ脂質又はポリマーが、ポリ(β-アミノエステル)、ポリ(L-リジン)、ポリ(エチレンイミン)(PEI)、ポリ(アミドアミン)デンドリマー(PAMAM)、アミン・エステル共重合体、ポリ(メタクリル酸ジメチルアミノエチル)(PDMAEMA)、キトサン、L-ラクチド・L-リジン共重合体、ポリ[α-(4-アミノブチル)-L-グリコール酸](PAGA)又はポリ(4-ヒドロキシ-L-プロリンエステル)(PHP)を含む、請求項87に記載の合成ナノ担体。
- 前記コーティングが、中性又は負電荷をもつ脂質又はポリマーを含む、請求項70に記載の合成ナノ担体。
- 前記中性又は負電荷をもつコーティングが、ポリグルタミン酸(PGA)、ポリ(アクリル酸)、アルギン酸又はコレステリルヘミサクシネート/1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミンを含む、請求項89に記載の合成ナノ担体。
- 前記中性又は負電荷をもつコーティングが双性イオン型ポリマーを含む、請求項89に記載の合成ナノ担体。
- 前記中性又は負電荷をもつコーティングがリポソームを含む、請求項89に記載の合成ナノ担体。
- 前記リポソームが、1,2-ジオレオイル-3-トリメチルアンモニウムプロパン(DOTAP)、1,2-ジ-O-オクタデセニル-3-トリメチルアンモニウムプロパン(DOTMA)、3β-[N-(N’,N’-ジメチルアミノエタン)-カルバモイル]コレステロール(DC-Chol)、ジオクタデシルアミドグリシルスペルミン(DOGS)、コレステロール、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)又は1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)を含む、請求項92に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、CD4及び/又はCD8と選択的に結合する、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含む、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体のscFv断片から選択される結合ドメインを含む、請求項70に記載の合成ナノ担体。
- 前記担体が、ポリ(β-アミノエステル)を含む、請求項70に記載の合成ナノ担体。
- 前記コーティングが、ポリグルタミン酸(PGA)を含む、請求項70に記載の合成ナノ担体。
- 前記選択された細胞ターゲティングリガンドが、CD4抗体及び/又はCD8抗体から選択される結合ドメインを含み、前記担体が、ポリ(β-アミノエステル)を含み、前記コーティングが、ポリグルタミン酸(PGA)を含む、請求項70に記載の合成ナノ担体。
- 請求項70に記載の合成ナノ担体を含有する組成物。
- 治療を必要とする対象の治療方法であって、治療有効量の、請求項70に記載のナノ担体又は、請求項100に記載の組成物を投与することにより、治療を必要とする前記対象を治療する、前記方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110121336A (zh) | 2017-01-05 | 2019-08-13 | 弗莱德哈钦森癌症研究中心 | 改善疫苗功效的系统和方法 |
KR20200018645A (ko) | 2017-06-15 | 2020-02-19 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 표적화된 비-바이러스 dna 삽입 |
IL274179B2 (en) | 2017-10-27 | 2024-02-01 | Univ California | Targeted replacement of endogenous T cell receptors |
CN108383914A (zh) * | 2018-02-23 | 2018-08-10 | 北京美康基免生物科技有限公司 | 一种基于cd19的嵌合抗原受体及其应用 |
WO2019213308A1 (en) * | 2018-05-01 | 2019-11-07 | Fred Hutchinson Cancer Research Center | Nanoparticles for gene expression and uses thereof |
EP3968992A4 (en) * | 2019-05-15 | 2023-06-21 | Stemcyte, Inc. | PACKAGING AND SHIPPING HIGH CONCENTRATION CELLS |
SE544015C2 (en) * | 2019-06-18 | 2021-11-02 | Tx Medic Ab | Allogenic car-t cell therapy |
CN111925448B (zh) * | 2020-08-03 | 2022-06-21 | 山东大学 | 在体生成car-巨噬细胞的制备方法及肿瘤免疫治疗中的应用 |
GB202017555D0 (en) * | 2020-11-06 | 2020-12-23 | Harbour Antibodies Bv | Antibody-conjugated nanoparticles |
CN112870370A (zh) * | 2021-03-05 | 2021-06-01 | 广州贝奥吉因生物科技股份有限公司 | 一种基于黑磷纳米片的靶向载药体系及其制备方法 |
KR20240099259A (ko) | 2021-10-14 | 2024-06-28 | 아스널 바이오사이언시스, 인크. | 공동 발현된 shrna 및 논리 게이트 시스템을 갖는 면역 세포 |
CN114246986B (zh) * | 2021-12-29 | 2022-08-23 | 中国人民解放军陆军军医大学 | 一种基于原位调控免疫反应的心血管植入物及其制备方法 |
WO2023201097A1 (en) * | 2022-04-15 | 2023-10-19 | Turn Biotechnologies, Inc. | Methods and compositions for immune cell rejuvenation and therapies using rejuvenated immune cells |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63503138A (ja) * | 1986-02-25 | 1988-11-17 | センタ−、フォア、モレキュラ−、メディシン、アンド、イミュノロジ− | 診断および治療用抗体複合体 |
JP2002544173A (ja) * | 1999-05-10 | 2002-12-24 | イムノメディクス, インコーポレイテッド | 抗cd22抗体を用いたb細胞悪性腫瘍の免疫療法 |
JP2007504353A (ja) * | 2003-05-28 | 2007-03-01 | マサチューセッツ インスティチュート オブ テクノロジー | 生分解性ポリ(β−アミノエステル)およびその使用 |
WO2008109806A2 (en) * | 2007-03-08 | 2008-09-12 | Massachusetts Institute Of Technology | Electrostatic coating of particles for drug delivery |
JP2010501163A (ja) * | 2006-08-18 | 2010-01-21 | ノバルティス アーゲー | Prlr特異的抗体およびその使用 |
WO2014153114A1 (en) * | 2013-03-14 | 2014-09-25 | Fred Hutchinson Cancer Research Center | Compositions and methods to modify cells for therapeutic objectives |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US527016A (en) | 1894-10-02 | Worth | ||
US1999A (en) | 1841-03-12 | Improvement in seed-planters | ||
US3753357A (en) | 1970-12-14 | 1973-08-21 | Ovitron Res Corp | Method and apparatus for the preservation of cells and tissues |
US4078052A (en) | 1976-06-30 | 1978-03-07 | The United States Of America As Represented By The Secretary Of Health, Education And Welfare | Large unilamellar vesicles (LUV) and method of preparing same |
CH624011A5 (ja) | 1977-08-05 | 1981-07-15 | Battelle Memorial Institute | |
CH621479A5 (ja) | 1977-08-05 | 1981-02-13 | Battelle Memorial Institute | |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4241046A (en) | 1978-11-30 | 1980-12-23 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4199022A (en) | 1978-12-08 | 1980-04-22 | The United States Of America As Represented By The Department Of Energy | Method of freezing living cells and tissues with improved subsequent survival |
US4559298A (en) | 1982-11-23 | 1985-12-17 | American National Red Cross | Cryopreservation of biological materials in a non-frozen or vitreous state |
US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5866322A (en) * | 1988-01-29 | 1999-02-02 | Abbott Laboratories | Method for performing Rubella assay |
US6291158B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
US6291161B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertiore |
US5475096A (en) | 1990-06-11 | 1995-12-12 | University Research Corporation | Nucleic acid ligands |
US5496938A (en) | 1990-06-11 | 1996-03-05 | Nexstar Pharmaceuticals, Inc. | Nucleic acid ligands to HIV-RT and HIV-1 rev |
US5527894A (en) | 1990-06-11 | 1996-06-18 | Nexstar Pharmacueticals, Inc. | Ligands of HIV-1 tat protein |
US5270160A (en) | 1990-12-21 | 1993-12-14 | Toray Industries, Inc. | Polyester film and photosensitive material |
US5756291A (en) | 1992-08-21 | 1998-05-26 | Gilead Sciences, Inc. | Aptamers specific for biomolecules and methods of making |
ATE529444T1 (de) | 1994-01-11 | 2011-11-15 | Dyax Corp | Inhibitoren des humanplasmins, die sich von den kunitz domänen ableiten |
AUPP221098A0 (en) | 1998-03-06 | 1998-04-02 | Diatech Pty Ltd | V-like domain binding molecules |
DE602005022595D1 (de) | 2004-06-29 | 2010-09-09 | Immunocore Ltd | Einen modifizierten t-zellen-rezeptor exprimierende zellen |
US8663599B1 (en) * | 2004-10-05 | 2014-03-04 | Gp Medical, Inc. | Pharmaceutical composition of nanoparticles |
SI1772465T1 (sl) | 2005-01-05 | 2009-06-30 | F Star Biotech Forsch & Entw | Sintetične imunoglobulinske domene z modificiranimi vezavnimi lastnostmi v regijah molekule, ki se razlikujejo od komplementarnost dolučujočih regij |
GB0504767D0 (en) | 2005-03-08 | 2005-04-13 | Ares Trading Sa | Lipocalin protein |
EP1829895A1 (en) | 2006-03-03 | 2007-09-05 | f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. | Bispecific molecule binding TLR9 and CD32 and comprising a T cell epitope for treatment of allergies |
WO2007145227A1 (ja) | 2006-06-14 | 2007-12-21 | Chugai Seiyaku Kabushiki Kaisha | 造血幹細胞増加促進剤 |
CA2700391A1 (en) | 2007-09-24 | 2009-04-02 | University Of Zuerich | Designed armadillo repeat proteins |
PE20100362A1 (es) | 2008-10-30 | 2010-05-27 | Irm Llc | Derivados de purina que expanden las celulas madre hematopoyeticas |
US20120192298A1 (en) * | 2009-07-24 | 2012-07-26 | Sigma Aldrich Co. Llc | Method for genome editing |
AU2010327998B2 (en) * | 2009-12-10 | 2015-11-12 | Iowa State University Research Foundation, Inc. | TAL effector-mediated DNA modification |
GB201006096D0 (en) * | 2010-04-13 | 2010-05-26 | Alligator Bioscience Ab | Novel compositions and uses thereof |
CN102851304A (zh) * | 2011-06-30 | 2013-01-02 | 复旦大学 | 基于静电包衣的三元非病毒核酸递释系统及其制备方法 |
US9828582B2 (en) * | 2013-03-19 | 2017-11-28 | Duke University | Compositions and methods for the induction and tuning of gene expression |
DK3004338T3 (en) * | 2013-05-31 | 2019-04-08 | Cellectis Sa | LAGLIDADG HOMING ENDONUCLEASE DIVERSE T-CELL RECEPTOR ALPHA GENET AND APPLICATIONS THEREOF |
AU2017368320A1 (en) | 2016-12-02 | 2019-05-02 | Cartesian Therapeutics, Inc. | Cancer immuno therapy with highly enriched CD8+ chimeric antigen receptor T cells |
CN110121336A (zh) | 2017-01-05 | 2019-08-13 | 弗莱德哈钦森癌症研究中心 | 改善疫苗功效的系统和方法 |
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- 2017-04-14 CR CR20180503A patent/CR20180503A/es unknown
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-
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- 2018-10-11 CL CL2018002905A patent/CL2018002905A1/es unknown
- 2018-10-12 MX MX2022006948A patent/MX2022006948A/es unknown
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-
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- 2022-06-27 JP JP2022102442A patent/JP2022130552A/ja active Pending
- 2022-11-23 AU AU2022275453A patent/AU2022275453A1/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63503138A (ja) * | 1986-02-25 | 1988-11-17 | センタ−、フォア、モレキュラ−、メディシン、アンド、イミュノロジ− | 診断および治療用抗体複合体 |
JP2002544173A (ja) * | 1999-05-10 | 2002-12-24 | イムノメディクス, インコーポレイテッド | 抗cd22抗体を用いたb細胞悪性腫瘍の免疫療法 |
JP2007504353A (ja) * | 2003-05-28 | 2007-03-01 | マサチューセッツ インスティチュート オブ テクノロジー | 生分解性ポリ(β−アミノエステル)およびその使用 |
JP2010501163A (ja) * | 2006-08-18 | 2010-01-21 | ノバルティス アーゲー | Prlr特異的抗体およびその使用 |
WO2008109806A2 (en) * | 2007-03-08 | 2008-09-12 | Massachusetts Institute Of Technology | Electrostatic coating of particles for drug delivery |
WO2014153114A1 (en) * | 2013-03-14 | 2014-09-25 | Fred Hutchinson Cancer Research Center | Compositions and methods to modify cells for therapeutic objectives |
Non-Patent Citations (2)
Title |
---|
EXPERT OPIN DRUG DELIV, 2010 APR, vol. vol. 7, no. 4, pp. 535-550, JPN6021020477, 2010, pages 535 - 550, ISSN: 0005129123 * |
NAT NANOTECHNOL, 2017 AUG (EPUB 2017 APR 17), vol. 12, no. 8, JPN6021020480, 2017, pages 813 - 820, ISSN: 0005129124 * |
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