JP7510348B2 - 腫瘍特異的細胞枯渇のための抗cd25 - Google Patents
腫瘍特異的細胞枯渇のための抗cd25 Download PDFInfo
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Description
配列番号1のアミノ酸配列を含む可変重鎖と配列番号4のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号1のアミノ酸配列を含む可変重鎖と配列番号5のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号1のアミノ酸配列を含む可変重鎖と配列番号6のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号1のアミノ酸配列を含む可変重鎖と配列番号7のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号2のアミノ酸配列を含む可変重鎖と配列番号4のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号2のアミノ酸配列を含む可変重鎖と配列番号5のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号2のアミノ酸配列を含む可変重鎖と配列番号6のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号2のアミノ酸配列を含む可変重鎖と配列番号7のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号3のアミノ酸配列を含む可変重鎖と配列番号4のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号3のアミノ酸配列を含む可変重鎖と配列番号5のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
配列番号3のアミノ酸配列を含む可変重鎖と配列番号6のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、及び、
配列番号3のアミノ酸配列を含む可変重鎖と配列番号7のアミノ酸配列を含む可変軽鎖とを含む抗体又は抗原結合フラグメント、
からなる群から選択される。
a. i)配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号4のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号4のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
b. i)配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号5のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号5のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
c. i)配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号6のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号6のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
d. i)配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号1のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号7のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号7のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
e. i)配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号4のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号4のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
f. i)配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号5のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号5のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
g. i)配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号6のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号6のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
h. i)配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号2のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号7のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号7のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
i. i)配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号4のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号4のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
j. i)配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号5のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号5のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
k. i)配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号6のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号6のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、又は、
l. i)配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変重鎖領域配列、若しくは配列番号3のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変重鎖領域配列、及び/又は、
ii)配列番号7のアミノ酸配列(又はその親和性成熟変異体等のその変異体)を含む可変軽鎖領域配列、若しくは配列番号7のアミノ酸配列(又はその親和性成熟変異体等のその変異体)に対して少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%、少なくとも96%、少なくとも97%、少なくとも98%若しくは少なくとも99%の配列同一性を有する可変軽鎖領域配列、
を含む抗CD25抗体剤(すなわち、抗体又はその抗原結合フラグメント)を提供する。
a. 配列番号1の可変重鎖配列及び配列番号4の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
b. 配列番号1の可変重鎖配列及び配列番号5の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
c. 配列番号1の可変重鎖配列及び配列番号6の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
d. 配列番号1の可変重鎖配列及び配列番号7の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
e. 配列番号2の可変重鎖配列及び配列番号4の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
f. 配列番号2の可変重鎖配列及び配列番号5の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
g. 配列番号2の可変重鎖配列及び配列番号6の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
h. 配列番号2の可変重鎖配列及び配列番号7の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
i. 配列番号3の可変重鎖配列及び配列番号4の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
j. 配列番号3の可変重鎖配列及び配列番号5の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、
k. 配列番号3の可変重鎖配列及び配列番号6の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合するか、又は、
l. 配列番号3の可変重鎖配列及び配列番号7の変異軽鎖配列を含む親抗体を準備することと、抗体を親和性成熟に供することとを含み、親和性成熟抗体が親抗体よりも少なくとも20%高い親和性でCD25に結合する、
方法を提供する。
(a)Fcγ受容体に1を上回る活性化型対抑制型比(activatory to inhibitory ratio)(A/I)で結合し、及び/又は、
(b)FcγRIIbに結合するよりも高い親和性でFcγRI、FcγRIIc及びFcγRIIIaの少なくとも1つに結合する。
[項1]
配列番号1、配列番号2又は配列番号3のアミノ酸配列を含む可変重鎖領域を含む抗体又はその抗原結合フラグメント。
[項2]
配列番号4、配列番号5、配列番号6又は配列番号7のアミノ酸配列を含む可変軽鎖領域を含む、先行項に記載の抗体又はその抗原結合フラグメント。
[項3]
配列番号4、配列番号5、配列番号6又は配列番号7のアミノ酸配列を含む可変軽鎖領域を含む抗体又はその抗原結合フラグメント。
[項4]
a. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号4のアミノ酸配列を含む可変軽鎖領域、
b. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号5のアミノ酸配列を含む可変軽鎖領域、
c. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号6のアミノ酸配列を含む可変軽鎖領域、
d. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号7のアミノ酸配列を含む可変軽鎖領域、
e. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号4のアミノ酸配列を含む可変軽鎖領域、
f. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号5のアミノ酸配列を含む可変軽鎖領域、
g. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号6のアミノ酸配列を含む可変軽鎖領域、
h. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号7のアミノ酸配列を含む可変軽鎖領域、
i. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号4のアミノ酸配列を含む可変軽鎖領域、
j. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号5のアミノ酸配列を含む可変軽鎖領域、
k. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号6のアミノ酸配列を含む可変軽鎖領域、又は、
l. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号7のアミノ酸配列を含む可変軽鎖領域、
を含む、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項5]
モノクローナル抗体、ドメイン抗体、一本鎖抗体、Fabフラグメント、F(ab’)2フラグメント、一本鎖可変フラグメント(scFv)、scFv-Fcフラグメント、一本鎖抗体(scAb)又は単一ドメイン抗体である、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項6]
ヒト化又は完全ヒト抗原結合抗体である、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項7]
前記抗体がIgG1、IgG2、IgG3及びIgG4アイソタイプ抗体からなる群から選択される、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項8]
二重特異性抗体、多重特異性抗体、又は治療剤若しくは診断剤を更に含む免疫複合体に含まれる、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項9]
ヒトCD25の細胞外ドメインに結合する、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項10]
ヒトCD25を表面上に発現する細胞に結合し、抗CD25抗体剤である、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項11]
CD25へのインターロイキン-2(IL-2)の結合を阻害しない、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項12]
CD25を介したインターロイキン-2(IL-2)のシグナル伝達を阻害しない、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項13]
脱フコシル化された、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項14]
ヒトCD25のエピトープに特異的に結合し、該エピトープが配列番号8のアミノ酸150~163(YQCVQGYRALHRGP)又はアミノ酸166~180(SVCKMTHGKTRWTQP)に含まれる1つ以上のアミノ酸残基を含む、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項15]
前記エピトープが配列番号7のアミノ酸150~163(YQCVQGYRALHRGP)及び配列番号8のアミノ酸166~180(SVCKMTHGKTRWTQP)を含む、項14に記載の抗体又は抗原結合フラグメント。
[項16]
項1~15のいずれか一項に記載の抗体又はその抗原結合フラグメントの親和性成熟変異体。
[項17]
薬剤として使用される、先行項のいずれか一項に記載の抗体又はその抗原結合フラグメント。
[項18]
項1~16のいずれか一項に記載の抗体又はその抗原結合フラグメントをコードする核酸分子。
[項19]
項18に記載の核酸分子を含む核酸ベクター。
[項20]
項19に記載の核酸ベクターを含む宿主細胞。
[項21]
項1~16のいずれか一項に記載の抗体又はその抗原結合フラグメントを作製する方法であって、項20に記載の宿主細胞を培養することを含む、方法。
[項22]
項1~16のいずれか一項に記載の抗体又はその抗原結合フラグメントを含む組成物。
[項23]
薬学的に許容可能な担体又は賦形剤を更に含む、項22に記載の組成物。
[項24]
癌の治療に使用される、項22又は項23に記載の医薬組成物。
[項25]
癌の治療のための薬剤の製造における項1~16のいずれか一項に記載の抗体若しくはその抗原結合フラグメント又は項22若しくは23に記載の組成物の使用。
[項26]
被験体において癌を治療する方法であって、該被験体に項22又は項23に記載の組成物を有効量投与することを含む、方法。
[項27]
前記被験体に第2の作用物質を同時に又は任意の順序で順次に投与することを更に含む、項26に記載の方法。
[項28]
前記第2の作用物質が免疫チェックポイント阻害剤又は癌ワクチンである、項27に記載の方法。
[項29]
前記第2の作用物質が免疫チェックポイント阻害剤であり、該免疫チェックポイント阻害剤がPD-1アンタゴニストである、項28に記載の方法。
[項30]
前記PD-1アンタゴニストが抗PD-1抗体又は抗PD-L1抗体である、項29に記載の方法。
[項31]
前記被験体が固形腫瘍を有する、項26~30のいずれか一項に記載の方法。
[項32]
前記被験体が血液癌腫瘍を有する、項26~30のいずれか一項に記載の方法。
[項33]
被験体において腫瘍中の制御性T細胞を枯渇させる方法であって、項22又は項23に記載の組成物を有効量投与する工程を含む、方法。
[項34]
前記被験体が固形腫瘍を有する、項33に記載の方法。
[項35]
前記被験体が血液癌を有する、項33に記載の方法。
[項36]
容器内に項22又は項23に記載の組成物を含むキット。
[項37]
抗CD25抗体を作製する方法であって、項1~16のいずれか一項に記載の抗体を準備することと、該抗体を親和性成熟に供することと、項1~16のいずれか一項に記載の抗体よりも大きな親和性でCD25に結合する抗体を選択することとを含む、方法。
[項38]
医薬組成物を作製する方法であって、項37に記載の方法に従って作製された抗体を準備することと、該抗体と少なくとも1つ以上の薬学的に許容可能な賦形剤とを共配合することとを含む、方法。
表1に記載の重鎖及び軽鎖配列を有する抗体1、抗体2、抗体3、抗体4、抗体5、抗体6、抗体7、抗体8、抗体9、抗体10、抗体11及び抗体12と指定される抗体を、当該技術分野で標準的な技法を用いて生成した。
抗体を合成し、ヒトIgG1としてクローニングした。抗体を哺乳動物細胞(HEK293)において発現させた。細胞に重鎖及び軽鎖発現ベクターを一時的にトランスフェクトし、更に6日間~14日間培養した。適切な量の細胞にトランスフェクトし、およそ1mgの抗体を得た。培養物を採取し、アフィニティークロマトグラフィーを用いて一段階精製を行った。ヒトIgG1抗体を下記のように更に特性評価した。
ヒトCD25配列(Uniprot記録番号P01589)を示す様々な直鎖、単一ループ、βターン模倣体、ジスルフィド架橋模倣体、不連続ジスルフィド架橋体、不連続エピトープ模倣体のペプチドのセットを、固相Fmoc合成を用いて合成した(Pepscan BV, The Netherlands;Timmermann P et al., 2007 J. Mol. Recognit., 20, 283-99、Langedijk JP et al., 2011, Analytical Biochemistry. 417: 149-155)。合成ペプチドの各々への抗体の結合を、ELISA(Pepscan,The Netherlands)において試験した。ペプチドアレイを一次抗体溶液と共にインキュベートした(4℃で一晩)。洗浄後に、ペプチドアレイを1000倍希釈の適切な抗体ペルオキシダーゼコンジュゲート(2010-05;Southern Biotech)と共に25℃で1時間インキュベートした。洗浄後に、ペルオキシダーゼ基質2,2’-アジノ-ジ-3-エチルベンズチアゾリンスルホネート(ABTS)及び20μl/mlの3%H2O2を添加した。1時間後に発色を測定した。発色を電荷結合素子(CCD)カメラ及び画像処理システムで定量化した。CCDカメラにより得られた値は、標準96ウェルプレートELISAリーダーと同様、0mAU~3000mAUの範囲である。合成ペプチドの品質を検証するために、別個の陽性及び陰性対照ペプチドのセットを並行して合成し、非関連対照抗体を用いてスクリーニングした。
抗体を特性評価し、非IL-2遮断抗体に対するエピトープを決定した。抗ヒトCD25抗体である抗体1~抗体12についてのエピトープマッピングの結果を表2に示す。
抗体をKarpas299細胞への結合について評価する。CD25発現Karpas299細胞への結合を、Karpas299細胞を30μg/ml抗体の濃度から開始する試験物(抗CD25一次抗体)、続いて片対数希釈系列(7点)を用いて氷上で30分間染色することによって試験する。これに続いて、濃度1μg/mlの二次抗体(Alexa Fluor 647-AffiniPure F(ab’)2 Fragmentウサギ抗ヒトIgG Fcγフラグメント(Jackson ImmunoResearch))を用いて氷上で30分間染色する。全てのサンプルを二連で染色する。生細胞をサンプル取得時にフローサイトメトリーによってFSC対SSCのパラメーターを用いてゲーティングする。染色細胞の平均蛍光強度(MFI)をXYチャート上にプロットし、MFIを濃度の対数に対してグラフ化し、データを非線形回帰曲線にフィッティングし、それによりEC50を算出する。結果を図3に示す。
抗ヒトCD25抗体に対する親和性を、CM-5センサーチップを用いるBiacore 2000でのSPRによって25℃の周囲実験温度でそれらのKDを測定することによって決定した。抗ヒト抗体を、初めに全フローセルにわたって分析バッファー(pH7.4、10mM HEPES、150mM NaCl、3mM EDTA、0.05%Tween 20)中で12000~14000のRUまで10分かけて固定化した。リガンド(抗体試験物)を、続いて145RU~190RUの捕捉レベルまでロードした。次いで、分析物(hisタグ付き組換えヒトCD25)を、分析バッファー中にて400nMから開始して3.13nMの最低濃度までの2倍希釈で6分間会合させた。解離を分析バッファー中で10分間にわたって行った。サンプル濃度間の再生工程は、10mMグリシン(pH1.7)中で10分間行った。25μl/分の流量を、プロセス全体を通して維持した。動態データを、グローバル1:1 Langmuirモデルを用いて参照サブトラクション(reference subtraction)によりフィッティングした。結果を図4(A)~図4(L)に示す。
抗体競合を、標準逐次結合アッセイを用いてForte Bio Octet Red96システム(Pall Forte Bio Corp.,USA)で行った。26.8nM hisタグ付き組換えヒトCD25をNi-NTAバイオセンサー上に200秒間ロードした。動態バッファーに対するベースライン工程後に、センサーを66.6nMの第1の抗体に600秒間、続いて第2の抗CD25抗体(同様に66.6nMで600秒間)に曝露した。Forte BioのData Analysis Software 9.0を用いてデータを処理した。第2の抗体による追加の結合は、非占有エピトープを示し(エピトープについての競合なし)、結合がなければエピトープ遮断が示される(エピトープについての競合)。結果を図5に示す。
IL-2遮断を、STAT5リン酸化アッセイを用いて特性評価し、IL-2シグナル伝達を試験する。予め凍結したPBMC(Stemcell Technologies)をU字底96ウェルプレートにおいて10μg/ml抗CD25抗体の存在下で30分間培養した後、10%FBS(Sigma)、2mM L-グルタミン(Life Technologies)及び10000U/ml Pen-Strep(Sigma)を含有するRPMI 1640(Life Technologies)中で10U/mlのIL-2(Peprotech)を10分間添加する。細胞をeBioscience(商標) Foxp3/Transcription Factor Staining Buffer Set(Invitrogen)で固定及び透過処理し、BD Phosflow Perm Buffer III(BD Biosciences)で処理することでIL-2誘導STAT5リン酸化を停止する。次いで、細胞を表面及び細胞内蛍光色素標識抗体(STAT5-Alexa Fluor 647クローン47/stat5/pY694(BD Bioscience)、CD3-PerCP-Cy5.5クローンUCHT1(Biolegend)、CD4-BV510クローンSK3(BD Bioscience)、CD8-Alexa Fluor 700クローンRPA-T8(Invitrogen)、CD45RA-PE-Cy7クローンHI100(Invitrogen)、FoxP3-Alexa Fluor 488クローン236A/E7(Invitrogen))で同時に染色し、サンプルをFortessa LSR X20フローサイトメーター(BD Bioscience)で取得し、BD FACSDIVAソフトウェアを用いて分析する。FCS-H対FCS-Aを用いてダブレットを除外し、SSC-A対FCS-Aパラメーターを用いてリンパ球を規定する。CD3+T細胞を、CD3 PerCP-Cy5.5-A対FCS-Aのプロットを用いて規定し、ゲートをカウント対STAT5 Alexa Fluor 647-Aを示すヒストグラム上に描画して、STAT5+CD3+T細胞の集団を決定する。IL-2シグナル伝達の遮断率は、以下のように算出する:遮断(%)=100×[(Stat5+細胞無Ab群(%)-Stat5+細胞10μg/ml Ab群(%))/(Stat5+細胞無Ab群(%))]。異なるT細胞サブセット(CD4+、CD8+、CD4+FoxP3+、ナイーブ及びメモリーT細胞)によるSTAT5リン酸化の更なる分析も、それぞれのサブセットについてゲーティングすることによって評定し、上記のように分析することができる。グラフ化及び統計分析を、GraphPad Prism v7を用いて行う。
Teff応答へのIL-2シグナル伝達の影響を、細胞内グランザイムB(GrB)の上方調節及び増殖を試験する、T細胞活性化アッセイにおいて特性評価する。予め凍結した初代ヒト汎T細胞(Stemcell Technologies)を、eFluor450細胞増殖色素(Invitrogen)で製造業者の推奨に従って標識し、10%FBS(Sigma)、2mM L-グルタミン(Life Technologies)及び10000U/ml Pen-Strep(Sigma)を含有するRPMI 1640(Life Technologies)の入ったU字底96ウェルプレートに1×105細胞/ウェルで添加する。次いで、細胞を10μg/ml抗CD25抗体又は対照抗体、続いてHuman T-Activator CD3/CD28(20:1の細胞対ビーズ比;Gibco)で処理し、37℃の5%CO2加湿インキュベーター内で72時間インキュベートする。T細胞活性化を評定するために、細胞をeBioscience Fixable Viability Dye efluor780(Invitrogen)、続いて表面T細胞マーカーに対する蛍光色素標識抗体(CD3-PerCP-Cy5.5クローンUCHT1(Biolegend)、CD4-BV510クローンSK3(BD Bioscience)、CD8-Alexa Fluor 700クローンRPA-T8(Invitrogen)、CD45RA-PE-Cy7クローンHI100(Invitrogen)、CD25-BUV737クローン2A3(BD Bioscience))で染色した後、eBioscience(商標) Foxp3/Transcription Factor Staining Buffer Set(Invitrogen)で固定及び透過処理し、その後、細胞内GrB及び核内FoxP3について染色する(グランザイムB-PEクローンGB11(BD Bioscience)、FoxP3-APCクローン236A/E7)。サンプルをFortessa LSR X20フローサイトメーター(BD Bioscience)で取得し、BD FACSDIVAソフトウェアを用いて分析する。FCS-H対FCS-Aを用いてダブレットを除外し、SSC-A対FCS-Aパラメーターを用いてリンパ球を規定する。生CD3+リンパ球からゲーティングしたCD4+及びCD8+T細胞サブセットを、GrB-PE-A対増殖eFluor450-Aのプロットを用いて評定する。結果を全CD4+T細胞集団からの増殖性GrB陽性細胞のパーセンテージとして提示する。グラフ化及び統計分析を、GraphPad Prism v7を用いて行う(結果は示していない)。
抗体依存性細胞介在性細胞傷害アッセイ(ADCCアッセイ)を、抗ヒトCD25抗体の特性評価のために、低IgG FBS添加培地(RPMI中4%FBS)中で異なる濃度の抗ヒトCD25抗体と共に37℃で20分間インキュベートしたCD25発現SR786細胞(本明細書では標的(T)細胞と呼ばれる)を用いて行った。次いで、ADCCエフェクター(E)細胞を細胞-mAb混合物に1:1のE:T比で添加する。エフェクター細胞は、ルシフェラーゼレポーター系が安定にトランスフェクトされ、CD16/FcγRIIIAを過剰発現するJurkat細胞(Promega)である。37℃で一晩のインキュベーション後に、細胞を溶解させ、ルシフェラーゼ活性を、特異的ルシフェラーゼ基質の加水分解による発光放出を用い、製造業者の説明書(PromegaのBio-Glowプロトコル)に従って測定する。生データのグラフを、Graphpad Prism v7を用いて作成し、用量応答曲線を生成する。相対発光量(RLU)を抗体濃度の対数に対してXYチャート上にプロットし、データを非線形回帰曲線にフィッティングし、それによりEC50を算出する。
また、抗体依存性細胞介在性食作用(ADCP)アッセイを、in vitro分化Tregを標的細胞として用い、単球由来マクロファージをエフェクター細胞として用いて行った。PBMCを、フィコール勾配遠心分離によって白血球コーンから単離した。単球(CD14+細胞)を、CD14マイクロビーズ(Miltenyi Biotec)を用いて単離した。単球を10%FBS(Sigma)、2mM L-グルタミン(Life Technologies)及び10000U/ml Pen-Strep(Sigma)を含有するRPMI 1640(Life Technologies)中、50ng/ml M-CSFの存在下で5日間培養し、M-CSFを含有する新鮮培地を3日後に添加した。制御性T細胞(Treg)を、Human Treg Cell Differentiation Kit(R&D Systems)を用いて単離した。これらの細胞を37℃の5%CO2加湿インキュベーター内で5日間インキュベートし、eFluor450色素(Invitrogen)で製造業者の推奨に従って標識した。5日目に、マクロファージ及びeFluor450色素標識Tregを、下記のように抗CD25抗体又は対照の存在下にて10対1のエフェクター対標的比で4時間同時培養する。10対1のエフェクター対標的比のために、標的細胞(Treg)を1×104細胞/ウェルで添加し、エフェクター細胞(マクロファージ)を1×105細胞/ウェルで添加した。次いで、抗CD25抗体を1μg/mlの最高濃度、続いて対数系列(7点)にて二連で添加した。細胞及び抗体を37℃、5%CO2で4時間インキュベートした。ADCPを評定するために、細胞を氷上に置き、細胞表面マーカーCD14(CD14-PerCP-Cy5.5クローンMfP9(BD Biosciences))で染色し、eBioscience固定バッファーで固定した。二色フローサイトメトリー分析を、Fortessa LSR X20を用いて行った。残留標的細胞は、eFluor450色素+/CD14-である細胞と規定した。マクロファージは、CD14+として規定した。二重標識細胞(eFluor450色素+/CD14+)は、マクロファージによる標的の食作用を表すとみなした。標的細胞の食作用は、以下の式を用いて算出した:食作用(%)=100×[(二重陽性率)/(二重陽性率+残留標的率)]。
実施例1において特定された抗体を、IL-2シグナル伝達を妨げない能力及びCD25発現標的細胞を殺傷する能力に関して更に評価した。STAT5アッセイにより、試験した抗体が、試験したIL-2濃度に関わらずにIL-2シグナル伝達を遮断せず、参照抗体ダクリズマブによってIL-2シグナル伝達が完全に遮断されることが示された(図6)。競合アッセイにより、抗体10がダクリズマブ又はバシリキシマブと競合しないことが示された(図5)。いわゆる「Tac」エピトープを介したCD25とIL-2との相互作用を遮断することが示されているダクリズマブ(非特許文献17及び非特許文献18)、及びバシリキシマブは、抗体10とは異なるエピトープに結合する(図5)。これにより、STAT5リン酸化アッセイにおいてダクリズマブがIL-2シグナル伝達を遮断し、抗体2がIL-2シグナル伝達を遮断しない理由を説明することができる(図6)。最後に、抗体は、IgG1アイソタイプ又はFc silent CD25標的抗体と比較して、CD25発現癌細胞に対するADCC(図7)及びADCPを介したヒトマクロファージの殺傷(図8及び図9)を誘導する。
材料及び方法
非IL-2遮断抗体の治療活性:Charles Riverから入手した雌性BALB/cマウスに、0%マトリゲル中3×105個のCT26腫瘍細胞を脇腹に皮下注射した(1群当たりn=15)。動物を1日目の体重に基づいて処理群に無作為化した。処理を6日目に開始し、マウスを200μg/動物の各抗体(マウスIgG2aアイソタイプ、IL-2中和抗体、マウスIgG1アイソタイプのIL-2シグナル伝達を遮断する抗マウスCD25であるPC61 mIgG1、及びマウスIgG2aアイソタイプのIL-2シグナル伝達を遮断しない抗マウスCD25である7D4 mIgG2a)の1回の注射で処理した。動物に抗体1つ当たり1群での単独療法処理、又は7D4 mIgG2aとIL-2中和抗体、若しくは7D4 mIgG2aとPC61 mIgG1抗体との併用処理を行った。マウスを、腫瘍体積が2000mm3に達した時点又は50日間のいずれか早い方で屠殺した。
抗CD25枯渇非IL-2遮断抗体7D4 mIgG2aは、処理マウスにおいて腫瘍拒絶を誘導し、他の抗体は、アイソタイプ対照マウスIgG2aと比較した場合に単独療法として効果を示さなかった。PC61 mIgG1又はIL2 nAbのいずれかのIL2遮断抗体との組合せは、非IL-2遮断抗体7D4 mIgG2aの治療活性を抑止する(図10)。これにより、7D4 mIgG2aの非IL-2遮断特徴が治療活性に重要であることが実証される。この抗体の治療活性が、最適活性についてIL-2シグナル伝達に依存するTエフェクター細胞によって媒介される抗腫瘍免疫応答に依拠することも示唆される。これらの結果から、IL-2/CD25遮断活性の欠如がCD25標的抗体の最適治療活性に必要とされ、癌療法における本明細書に記載の抗CD25非IL-2遮断抗体の使用を支持することが示される。
当業者には、本発明が実施例又は本明細書に含まれる或る特定の実施形態の他の記載ではなく、添付の特許請求の範囲によって定義されることが理解される。
参考文献
Beck A et al.,2017. Nat Rev Drug Discov. 16:315-337.
Bielekova B.,2013. Neurotherapeutics,10(1):55-67
Dantal J et al.,1991,Transplantation 52:110-5
Kearns JD et al.,2015. Mol Cancer Ther. 14:1625-36.
Kijanka M et al.,2015. Nanomedicine. 10:161-174.
Langedijk JP et al.,2011. Analytical Biochemistry. 417:149-155.
Liu L,2015. J Pharm Sci. 104:1866-84.
Liu Y et al.,2014. MAbs. 6:483-92.
Lowenthal J.W et al.,1985. J. Immunol.,135,3988-3994
Moreau,J.-L et al.,1987. Eur. J. Immunol. 17,929-935;
Onishi H et al;,2012 Anticanc. Res. 32,997-1003
Queen C et al.,1989. PNAS. 86(24):10029-10033
Redman JM et al.,2015. Mol Immunol. 67: 28-45.
Setiady Y et al.,2010. Eur J Immunol. 40:780-6),
Shang B et al.,2015,Sci Rep. 5:15179
Sliwkowski M & Mellman I,2013. Science. 341:1192-8.
Timmermann P et al.,2007,J. Mol. Recognit.,20,283-99.
Volk HD et al.,1989 Clin. exp. Immunol. 76,121-5
Vazquez-Lombardi R et al.,2015. Drug Discov Today. 20:1271-83.
Smyth M et al.,2014,Immunol Cell Biol. 92,473-4
Elpek et al.,2007 J Immunol. 178(11):6840-8.;
Golgher et al.,2002 Eur J Immunol. 32(11):3267-75;
Jones et al.,2002; Cancer Immun. 22;2:1
Onizuka et al.,1999 Cancer Res. 59(13):3128-33.;
Shimizu et al.,1999 J Immunol.163(10):5211-8
Hodi et al.,2008,Proc. Natl. Acad. Sci. USA,105,3005-3010
Quezada et al.,2006,J Clin Invest.116(7):1935-45
Vargas A et al.,2017,Immunity,46(4):577-586)
Kohm A et al.,2006,J Immunol. 176: 3301-5;
Hallett W et al.,2008. Biol Blood Marrow Transplant 14:1088-1099;
Fecci P et al.,2006 Clin Cancer Res. 12:4294-4305;
McNeill A et al.,2007. Scand J Immunol 65: 63-9;
Couper K et al.,2007. J Immunol. 178: 4136-4146;
O’Mahony D et al,2008,Blood,112(11),231;
Oh et al,2017,Oncotarget 8(29) 47440-4753;
Kreitman RJ et al,2016,Clin Cancer Res,22(2) 310-318;
Flynn MJ et al 2016,Mol Cancer Ther 15(11) 2709-2721;
Ellington et al. Nature. 1990; 346(6287): 818-822;
Tuerk et al.,Science. 1990; 249(4968):505-510;
Ni et al.,Curr Med Che 2011; 18(27):4206-14.
Altschul SF et al, 1997, Nucleic Acids Res. 25:33389-3402
Rajpal et al.,Proc Natl Acad Sci USA,2005,102(24):8466-71;
Steinwand et al.,MAbs,2014,6(1):204-18
Jarasch A et al; Pharm Sci. 2015 Jun;104(6):1885-1898
Claims (26)
- a)配列番号1、配列番号2又は配列番号3のアミノ酸配列を含む可変重鎖領域、及び
b)配列番号4、配列番号5、配列番号6又は配列番号7のアミノ酸配列を含む可変軽鎖領域、
を含む、抗CD25抗体又はその抗原結合フラグメント。 - a. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号4のアミノ酸配列を含む可変軽鎖領域、
b. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号5のアミノ酸配列を含む可変軽鎖領域、
c. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号6のアミノ酸配列を含む可変軽鎖領域、
d. 配列番号1のアミノ酸配列を含む可変重鎖領域及び配列番号7のアミノ酸配列を含む可変軽鎖領域、
e. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号4のアミノ酸配列を含む可変軽鎖領域、
f. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号5のアミノ酸配列を含む可変軽鎖領域、
g. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号6のアミノ酸配列を含む可変軽鎖領域、
h. 配列番号2のアミノ酸配列を含む可変重鎖領域及び配列番号7のアミノ酸配列を含む可変軽鎖領域、
i. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号4のアミノ酸配列を含む可変軽鎖領域、
j. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号5のアミノ酸配列を含む可変軽鎖領域、
k. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号6のアミノ酸配列を含む可変軽鎖領域、又は、
l. 配列番号3のアミノ酸配列を含む可変重鎖領域及び配列番号7のアミノ酸配列を含む可変軽鎖領域、
を含む、請求項1に記載の抗体又はその抗原結合フラグメント。 - モノクローナル抗体、Fabフラグメント、F(ab’)2フラグメント、一本鎖可変フラグメント(scFv)、scFv-Fcフラグメント、又は一本鎖抗体(scAb)である、請求項1又は2に記載の抗体又はその抗原結合フラグメント。
- 前記抗体がIgG1、IgG2、IgG3及びIgG4アイソタイプ抗体からなる群から選択される、請求項1~3のいずれか一項に記載の抗体又はその抗原結合フラグメント。
- 二重特異性抗体又は多重特異性抗体である、請求項1~4のいずれか一項に記載の抗体又はその抗原結合フラグメント。
- CD25へのインターロイキン-2(IL-2)の結合を阻害しない、請求項1~5のいずれか一項に記載の抗体又はその抗原結合フラグメント。
- CD25を介したインターロイキン-2(IL-2)のシグナル伝達を阻害しない、請求項1~6のいずれか一項に記載の抗体又はその抗原結合フラグメント。
- 脱フコシル化された、請求項1~7のいずれか一項に記載の抗体又はその抗原結合フラグメント。
- ヒトCD25のエピトープに特異的に結合し、該エピトープが配列番号8のアミノ酸150~163(YQCVQGYRALHRGP)及び配列番号8のアミノ酸166~180(SVCKMTHGKTRWTQP)を含む、請求項1~8のいずれか一項に記載の抗体又は抗原結合フラグメント。
- 治療剤又は診断剤、及び請求項1~9のいずれか一項に記載の抗体又はその抗原結合フラグメントを含む、免疫複合体。
- 薬剤として使用される、請求項1~9いずれか一項に記載の抗体若しくはその抗原結合フラグメント、又は請求項10に記載の免疫複合体。
- 請求項1~9のいずれか一項に記載の抗体又はその抗原結合フラグメントをコードする核酸分子。
- 請求項12に記載の核酸分子を含む核酸ベクター。
- 請求項13に記載の核酸ベクターを含む宿主細胞。
- 請求項1~9のいずれか一項に記載の抗体又はその抗原結合フラグメントを作製する方法であって、請求項14に記載の宿主細胞を培養することを含む、方法。
- 請求項1~9のいずれか一項に記載の抗体又はその抗原結合フラグメントを含む組成物。
- 薬学的に許容可能な担体又は賦形剤を更に含む、請求項16に記載の組成物。
- 癌の治療に使用される、請求項16又は請求項17に記載の組成物。
- 第2の作用物質が同時に又は任意の順序で順次に投与されることを更なる特徴とする、請求項18に記載の組成物。
- 前記第2の作用物質が免疫チェックポイント阻害剤又は癌ワクチンである、請求項19に記載の組成物。
- 前記第2の作用物質が免疫チェックポイント阻害剤であり、該免疫チェックポイント阻害剤がPD-1アンタゴニストである、請求項20に記載の組成物。
- 前記PD-1アンタゴニストが抗PD-1抗体又は抗PD-L1抗体である、請求項21に記載の組成物。
- 前記癌が血液癌腫瘍を含む、請求項18~22のいずれか一項に記載の組成物。
- 腫瘍中の制御性T細胞を枯渇させるための、請求項16又は請求項17に記載の組成物。
- 前記腫瘍が血液癌である、請求項24に記載の組成物。
- 容器内に請求項16又は請求項17に記載の組成物を含むキット。
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Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11371066B2 (en) | 2015-07-13 | 2022-06-28 | Modular Genetics, Inc. | Generation of acyl alcohols |
CN108795858A (zh) * | 2017-04-28 | 2018-11-13 | 深圳宾德生物技术有限公司 | 高抗癌活性t细胞的筛选方法和应用 |
JP2021515568A (ja) | 2018-03-13 | 2021-06-24 | タスク セラピューティクス リミテッド | 腫瘍特異的細胞枯渇のための抗cd25 |
CN114630838A (zh) * | 2019-05-20 | 2022-06-14 | 法国国家健康和医学研究院 | 新的抗cd25抗体 |
TW202138388A (zh) | 2019-12-30 | 2021-10-16 | 美商西根公司 | 以非海藻糖苷化抗-cd70抗體治療癌症之方法 |
US20230174670A1 (en) | 2020-05-14 | 2023-06-08 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Anti-cd25 antibodies, antigen-binding fragments thereof, and medical uses thereof |
AU2021378308A1 (en) * | 2020-11-13 | 2023-06-15 | Ibio, Inc. | Cd25 antibodies |
AU2021380966A1 (en) * | 2020-11-20 | 2023-06-22 | Alderaan Biotechnology | Anti-cd25 antibodies |
WO2022106663A1 (en) * | 2020-11-20 | 2022-05-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-cd25 antibodies |
JP2024508207A (ja) | 2020-12-02 | 2024-02-26 | ブイアイビー ブイゼットダブリュ | がんに対する組み合わせ治療におけるltbrアゴニスト |
JP2024505556A (ja) | 2021-02-02 | 2024-02-06 | ラクテン・メディカル,インコーポレイテッド | がん、腫瘍および腫瘍細胞の局所および全身処置のための方法 |
WO2022184615A1 (en) | 2021-03-01 | 2022-09-09 | F. Hoffmann-La Roche Ag | Novel biomarkers and uses thereof |
CN115724971A (zh) | 2021-08-09 | 2023-03-03 | 南京诺艾新生物技术有限公司 | 重组抗人cd25抗体及其应用 |
WO2023031403A1 (en) | 2021-09-02 | 2023-03-09 | F. Hoffmann-La Roche Ag | Antibodies for the treatment of aml |
AU2022337286A1 (en) * | 2021-09-03 | 2024-02-29 | Novarock Biotherapeutics, Ltd. | Bispecific binding proteins that bind cd137 and a tumor associated antigen |
WO2023134766A1 (zh) | 2022-01-17 | 2023-07-20 | 诺纳生物(苏州)有限公司 | 靶向cd25的抗体及其制备方法和应用 |
WO2023208990A1 (en) | 2022-04-26 | 2023-11-02 | F. Hoffmann-La Roche Ag | Combination therapy for the treatment of cancer comprising a fas axis antagonist and a t-reg cell depleting agent antagonist, |
CN115197321B (zh) * | 2022-06-02 | 2023-08-18 | 四川大学 | 靶向cd25的抗体及其用途 |
CN115181182B (zh) * | 2022-06-13 | 2024-03-29 | 南京融捷康生物科技有限公司 | 一种人源化的抗cd25的单域抗体及其应用 |
CN115181181B (zh) * | 2022-06-13 | 2024-03-29 | 南京融捷康生物科技有限公司 | 一种抗cd25的单域抗体及其应用 |
WO2024006965A1 (en) * | 2022-06-30 | 2024-01-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cd25-specific antibodies and uses thereof |
WO2024040194A1 (en) | 2022-08-17 | 2024-02-22 | Capstan Therapeutics, Inc. | Conditioning for in vivo immune cell engineering |
WO2024088987A1 (en) | 2022-10-26 | 2024-05-02 | F. Hoffmann-La Roche Ag | Combination therapy for the treatment of cancer |
CN118240080A (zh) * | 2022-12-22 | 2024-06-25 | 深圳市福元生物科技有限公司 | 一种cd25单域抗体、人源化抗体、及制备方法 |
WO2024165454A1 (en) | 2023-02-06 | 2024-08-15 | F. Hoffmann-La Roche Ag | Combination therapy and uses thereof |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4208479A (en) * | 1977-07-14 | 1980-06-17 | Syva Company | Label modified immunoassays |
US4578335A (en) * | 1984-05-21 | 1986-03-25 | Immunex Corporation | Interleukin 2 receptor |
CA2505991C (en) | 2002-11-15 | 2018-02-27 | Genmab A/S | Human monoclonal antibodies against cd25 |
WO2004063355A2 (en) | 2003-01-10 | 2004-07-29 | Protein Design Labs, Inc. | Novel methods of diagnosis of metastatic cancer, compositions and methods of screening for modulators of matastatic cancer |
JP2006517970A (ja) | 2003-02-14 | 2006-08-03 | ユニバーシティ オブ サザン カリフォルニア | 癌免疫療法のための組成物及び方法 |
WO2005123780A2 (en) | 2004-04-09 | 2005-12-29 | Protein Design Labs, Inc. | Alteration of fcrn binding affinities or serum half-lives of antibodies by mutagenesis |
GB0409799D0 (en) | 2004-04-30 | 2004-06-09 | Isis Innovation | Method of generating improved immune response |
US7696175B2 (en) | 2004-10-29 | 2010-04-13 | University Of Southern California | Combination cancer immunotherapy with co-stimulatory molecules |
GB0507696D0 (en) | 2005-04-15 | 2005-05-25 | Novartis Ag | Organic compounds |
WO2008003473A2 (en) | 2006-07-06 | 2008-01-10 | Merck Patent Gmbh | Compositions and methods for enhancing the efficacy of il-2 mediated immune responses |
KR101368596B1 (ko) * | 2006-08-18 | 2014-03-17 | 조마 테크놀로지 리미티드 | Prlr 특이적 항체 및 그 용도 |
EP1997832A1 (en) * | 2007-05-29 | 2008-12-03 | Ganymed Pharmaceuticals AG | Monoclonal antibodies against Claudin-18 for treatment of cancer |
RU2391401C2 (ru) | 2008-02-12 | 2010-06-10 | Общество с ограниченной ответственностью "Лаборатория клеточного мониторинга" | СПОСОБ ПОЛУЧЕНИЯ ПОПУЛЯЦИИ CD4+CD25+Foxp3+ Т-ЛИМФОЦИТОВ ЧЕЛОВЕКА ex vivo, СПОСОБ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ |
JP5882058B2 (ja) * | 2008-11-07 | 2016-03-09 | ファブラス エルエルシー | 組合せ抗体ライブラリー及びその使用 |
KR101545914B1 (ko) | 2009-09-22 | 2015-08-20 | 프로바이오겐 아게 | 특수화된 글리칸 구조를 함유하는 분자의 생산 방법 |
WO2011077245A2 (en) | 2009-12-23 | 2011-06-30 | Fondazione Centro San Raffaele Del Monte Tabor | Compositions |
TWI513466B (zh) | 2010-01-20 | 2015-12-21 | Boehringer Ingelheim Int | 抗凝血劑解毒劑 |
EP2378287A1 (en) * | 2010-04-15 | 2011-10-19 | TXCell | New method for isolating Tr1 cells |
EP2595657A4 (en) | 2010-07-22 | 2015-09-23 | Univ California | ANTITUMOR ANTIBODY ANTIBODIES AND METHODS OF USING SAME |
US9682143B2 (en) | 2012-08-14 | 2017-06-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
US20150010539A1 (en) * | 2013-03-15 | 2015-01-08 | Abbvie Biotherapeutics Inc. | Anti-cd25 antibodies and their uses |
DK2970486T3 (en) * | 2013-03-15 | 2018-08-06 | Xencor Inc | MODULATION OF T-CELLS WITH BISPECIFIC ANTIBODIES AND FC-FUSIONS |
CA2904527A1 (en) | 2013-03-15 | 2014-09-18 | Abbvie Biotechnology Ltd. | Anti-cd25 antibodies and their uses |
NZ714765A (en) * | 2013-06-06 | 2021-12-24 | Pf Medicament | Anti-c10orf54 antibodies and uses thereof |
WO2015109212A1 (en) * | 2014-01-17 | 2015-07-23 | Pfizer Inc. | Anti-il-2 antibodies and compositions and uses thereof |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
GB201403775D0 (en) * | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
BR112017000703A2 (pt) | 2014-07-16 | 2017-11-14 | Genentech Inc | métodos para tratar ou retardar a progressão do câncer, para reduzir ou inibir a reincidência do câncer, para tratar ou retardar a progressão da imunidade tumoral e para aumentar, intensificar ou estimular uma resposta ou função imune e kit |
ES2905301T3 (es) * | 2014-07-22 | 2022-04-07 | Apollomics Inc | Anticuerpos anti-PD-1 |
WO2016021720A1 (ja) | 2014-08-07 | 2016-02-11 | 学校法人兵庫医科大学 | Il-18と分子標的抗体とを併用する癌治療薬 |
US11147652B2 (en) | 2014-11-13 | 2021-10-19 | Align Technology, Inc. | Method for tracking, predicting, and proactively correcting malocclusion and related issues |
PL3221355T3 (pl) * | 2014-11-20 | 2021-03-08 | F. Hoffmann-La Roche Ag | Terapia skojarzona składająca się z dwuswoistych aktywujących limfocyty T cząsteczek wiążących antygen CD3 i receptor folianowy 1 (FolR1) oraz antagonistów wiązania osi PD-1 |
ES2786651T3 (es) | 2015-02-19 | 2020-10-13 | Compugen Ltd | Anticuerpos anti-PVRIG y métodos de uso |
RU2739163C2 (ru) * | 2015-03-23 | 2020-12-21 | Байер Фарма Акциенгезельшафт | Анти-сеасам6 антитела и их применения |
CA2946113A1 (en) * | 2015-10-23 | 2017-04-23 | Pfizer Inc. | Anti-il-2 antibodies and compositions and uses thereof |
US20170204154A1 (en) | 2016-01-20 | 2017-07-20 | Delinia, Inc. | Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases |
CN107922503B (zh) * | 2016-03-04 | 2018-08-28 | 四川科伦博泰生物医药股份有限公司 | 一种pdl-1抗体、其药物组合物及其用途 |
JP2019514844A (ja) * | 2016-03-04 | 2019-06-06 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗cd73抗体を用いた併用療法 |
AU2017247880B2 (en) | 2016-04-07 | 2024-07-11 | Cancer Research Technology Limited | Anti CD25 FC gamma receptor bispecific antibodies for tumor specific cell depletion |
EP4344748A3 (en) * | 2016-06-10 | 2024-06-12 | Regeneron Pharmaceuticals, Inc. | Anti-gitr antibodies and uses thereof |
JP6831651B2 (ja) | 2016-07-04 | 2021-02-17 | 川崎重工業株式会社 | ワークの袋詰め装置 |
CN110167957A (zh) | 2016-11-08 | 2019-08-23 | 德里尼亚公司 | 用于治疗自身免疫疾病的il-2变体 |
US11879014B2 (en) * | 2017-03-17 | 2024-01-23 | Tusk Therapeutics Ltd. | Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody |
WO2019005922A1 (en) | 2017-06-28 | 2019-01-03 | North Carolina State University | PHOTONIC PROHIBITED BAND RESONATOR FOR MAGNETIC RESONANCE APPLICATIONS |
WO2019008386A1 (en) | 2017-07-06 | 2019-01-10 | Tusk Therapeutics Ltd | COMPOUNDS AND METHODS FOR DEPLOYING SPECIFIC CELLS FROM A TUMOR |
JP2021515568A (ja) | 2018-03-13 | 2021-06-24 | タスク セラピューティクス リミテッド | 腫瘍特異的細胞枯渇のための抗cd25 |
MX2020008769A (es) | 2018-03-13 | 2020-10-08 | Tusk Therapeutics Ltd | Agentes anticuerpos anti-cd25. |
KR20200003558A (ko) | 2018-07-02 | 2020-01-10 | 휴렛-팩커드 디벨롭먼트 컴퍼니, 엘.피. | 용지 슬립을 방지하기 위한 급지장치 및 이를 포함하는 화상형성장치 |
KR102080909B1 (ko) | 2018-07-06 | 2020-02-24 | 한국수력원자력 주식회사 | 원자로의 해체 시스템 |
-
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