JP2018511320A - 治療およびエピトープマッピング用T細胞の感作および増殖のためのin vitro人工リンパ節法 - Google Patents
治療およびエピトープマッピング用T細胞の感作および増殖のためのin vitro人工リンパ節法 Download PDFInfo
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Abstract
Description
a)患者試料からのT細胞を、抗原特異的T細胞自己I型樹状細胞(DC1)とin vitroで共培養する工程と;
b)工程a)からの細胞をIL-7およびIL-5と接触させ、刺激された抗原特異的T細胞を生成する工程と;
c)その後、刺激された抗原特異的T細胞をIL-2と接触させ、それによって抗原特異性および細胞機能を維持する増殖した抗原特異的T細胞集団を生成する工程
とをさらに含む。
a)T細胞をHER2パルスDC1と共培養する工程と;
b)工程a)からの細胞をIL-7およびIL-15と接触させ、刺激された抗原特異的T細胞を生成する工程と;
c)その後、刺激された抗原特異的T細胞をIL-2と接触させ、それによって抗原特異性および細胞機能を維持する増殖した抗原特異的T細胞集団を生成する工程
とを含む。
ペプチド42-56:HLDMLRHLYQGCQVV(配列番号1);
ペプチド98-114:RLRIVRGTQLFEDNYAL(配列番号2);
ペプチド328-345:TQRCEKCSKPCARVCYGL(配列番号3);
ペプチド776-790:GVGSPYVSRLLGICL(配列番号4);
ペプチド927-941:PAREIPDLLEKGERL(配列番号5);および
ペプチド1166-1180:TLERPKTLSPGKNGV(配列番号6);
を含むHER2 MHCクラスIIペプチドでパルスされる。
他に定義されない限り、本明細書で使用される全ての技術用語および科学用語は、本開示の発明主題が属する技術分野の当業者によって一般的に理解されるのと同じ意味を有する。本明細書に記載のものと類似または等価な任意の方法および材料が本発明の実施形態の実施または試験において使用され得るが、好ましい方法および材料が記載される。
ペプチド42-56:HLDMLRHLYQGCQVV(配列番号1);
ペプチド98-114:RLRIVRGTQLFEDNYAL(配列番号2);および
ペプチド328-345:TQRCEKCSKPCARVCYGL(配列番号3);
を含み、
好ましいHER2 ICDペプチドは、
ペプチド776-790:GVGSPYVSRLLGICL(配列番号4);
ペプチド927-941:PAREIPDLLEKGERL(配列番号5);および
ペプチド1166-1180:TLERPKTLSPGKNGV(配列番号6);
を含む。
本発明の実施形態は、ネオアジュバント化学療法後に残存疾患を有し、抗HER2 1型Tヘルパー(Th1)細胞免疫不全および再発性疾患の重大なリスクを有するHER2+浸潤性乳がん(「IBC」)患者に関する。Dattaらによって、抗HER2 CD4+T細胞応答は、乳がん連続体に沿って徐々に減少することが示された - 健常ドナーおよび良性疾患患者では強壮な応答、HER2+非浸潤性乳管がんを患者では抑制反応、およびHER2+IBC患者ではほとんど反応しなかった。本明細書では、(A)アジュバント1型極性化樹状細胞(「DC1」)ワクチン接種と、(B)抗HER2 Th1免疫を回復するための養子T細胞移植用の抗原特異的t細胞を増殖する方法との役割について検討する。
HER2pos-乳がんにおける腫瘍形成性連続体にわたる抗HER2 CD4+Th1応答の進行性消失の同定に加えて、Dattaらによって教示されるように、HER2pos-浸潤性乳がんにおける抗HER2 Th1応答の抑制は、HER2-パルス1型極性化樹状細胞(「DC1」)ワクチン接種後に差次的に回復した。トラスツズマブおよび化学療法(「T/C」)によるHER2標的療法の後には、または外科的切除もしくは放射線などの他の標準的治療によってでは、抑制応答は回復しなかった。回復した抗HER2 Th1応答は、少なくとも約6ヶ月間またはかなり長い間持続するようである。
ネオアジュバント療法後に残存疾患を有するHER2+IBC患者に、アジュバントHER2パルスDC1ワクチン接種をした。ELISPOTでIFN-γ産生を測定することにより、HER2クラスIIペプチドでパルスしたPBMCから免疫応答を生成した。応答は、CD4+Th1応答の3つの測定基準で評価した:(1)全体的な抗HER2応答性(≧1のペプチドに応答する)、(2)反応性ペプチドの数(応答レパートリー)、および(3)6つのHER2ペプチドにわたる累積応答。ワクチン接種前のTh1応答を、ワクチン接種3ヶ月後および6ヶ月後の応答と比較した。
ペプチド42-56:HLDMLRHLYQGCQVV(配列番号1);
ペプチド98-114:RLRIVRGTQLFEDNYAL(配列番号2);
ペプチド328-345:TQRCEKCSKPCARVCYGL(配列番号3);
ペプチド776-790:GVGSPYVSRLLGICL(配列番号4);
ペプチド927-941:PAREIPDLLEKGERL(配列番号5);および
ペプチド1166-1180:TLERPKTLSPGKNGV(配列番号6);
を含む。
ペプチド369-377:KIFGSLAFL(配列番号7);および
ペプチド689-697:RLLQETELV(配列番号8)
を含む。
応答性:刺激を受けていないバックグラウンドを差し引いた後の実験ウェル中>20SFC/106細胞として定義される免疫応答を、ワクチン接種前には1人のIBC患者しか示さなかった。ワクチン接種前の結果と比較して、全てのワクチン接種を受けたIBC患者は、抗HER2 IFN-γposThl応答における>2倍の増加として定義される免疫応答を示した。
(方法)
in vitroで、HER2特異的Th1細胞を、HER2ペプチドパルスDC1との共培養によって生成し、IL-2単独またはIL-2、IL-7、およびIL-15を用いて増殖させた。続いて、Th1細胞を、反復HER2-ペプチドパルスDC1共培養または抗CD3/CD28刺激のいずれかによって増殖させた。増殖倍率を、以下のように定義した:(増殖後の#T細胞/増殖前の#T細胞);特異性は、抗原特異的IFN-γ産生によってELISAにより測定した。
増殖の前に、T細胞の供給源を被験体から得る。被験体の例には、ヒト、イヌ、ネコ、マウス、ラット、およびそれらのトランスジェニック種が含まれる。好ましくは、被験体はヒトである。T細胞は、末梢血単核細胞、骨髄、リンパ節組織、脾臓組織、および腫瘍を含む多くの供給源から得ることができる。本明細書の特定の実施形態では、当該技術分野で利用可能な任意の数のT細胞株を使用することができる。特定の実施形態では、当業者に知られている任意の数の技法、例えばフィコール分離などを使用して被験体から採取した血液単位から、T細胞を得ることができる。好ましい一実施形態では、個体の循環血液由来の細胞は、アフェレーシスまたは白血球除去療法によって得られる。アフェレーシス生成物は、典型的には、T細胞、単球、顆粒球、B細胞、他の有核白血球、赤血球および血小板を含むリンパ球を含有する。一実施形態では、アフェレーシスによって収集された細胞を洗浄して血漿画分を除去し、その後の処理工程のために細胞を適切な緩衝液または培地に入れることができる。一実施形態では、細胞をリン酸緩衝食塩水(PBS)で洗浄する。代替実施形態では、洗浄溶液はカルシウムを欠き、マグネシウムを欠いていてもよく、または全てではないにしても多くの2価陽イオンを欠いていてもよい。洗浄後、細胞を、様々な生体適合性緩衝液、例えば、Ca不含、Mg不含PBSに再懸濁してもよい。あるいは、アフェレーシス試料の望ましくない成分を除去し、細胞を培地に直接再懸濁してもよい。
一般に、本実施形態のT細胞を、リンパ節を複製する条件下で増殖する。一実施形態では、リンパ節の複製は、1つ以上の以下の要素を培養条件に供給することを含む:1型樹状細胞、IL-15、IL-7およびIL-2。一実施形態では、抗原特異的T細胞を、1つ以上の1型樹状細胞、IL-15、IL-7およびIL-2の存在下で増殖させることができる。
特定の実施形態では、T細胞の集団を最初に抗原、例えば腫瘍標的抗原と接触させ、次いで、1つ以上のDC、IL-15、IL-7、およびIL-2を含む本実施形態の混合物にさらす。特定の一実施形態では、特定の抗原を、単独で、またはアジュバントと組み合わせて、または樹状細胞にパルスして、患者にワクチン接種することにより抗原特異的T細胞を誘導する。本実施形態の刺激方法を使用した増殖で使用するための抗原特異的細胞は、in vitroで生成されてもよい。
一実施形態では、抗原特異的T細胞を増殖させるための組成物および方法が提供される。T細胞を、1つ以上のDC、IL-15、IL-7、およびIL-2と接触させることを含む工程によって、抗原特異的T細胞を増殖させることができる。増殖したT細胞を使用して、抗原特異的T細胞受容体(「TCR」)およびそれに由来するエピトープを同定することができる。例えば、増殖したT細胞由来のTCRをクローニングすることができる。クローニングされたTCRは、所望の疾患または障害を治療する特異的養子T細胞療法の開発に有望なツールを提示する。例えば、クローニングされたTCRを使用して、ワクチンに有用なペプチド/抗原を生成することができる。
T細胞エピトープペプチド/結合ペプチド/ペプチドは、タンパク質抗原に由来し得る短いペプチドである。細胞を提示する抗原は、表面MHC分子を介して抗原に直接結合することができ、および/または抗原を内在化し、それをMHC分子に結合する能力がある短い断片に処理することができる。MHCに結合するペプチドの特異性は、ペプチドと特定のMHC分子のペプチド結合溝との間の特異的相互作用に依存する。
抗原特異的T細胞を、毎日数回の頻度で動物に投与することができ、または1日1回、1週間に1回、2週間に1回、1ヶ月に1回などの低い頻度で、もしくは数ヶ月に1回、さらには1年に1回もしくはそれ以下などのさらにより低い頻繁で投与してもよい。投薬の頻度は、当業者には容易に明らかであり、限定されるものではないが、治療される疾患のタイプおよび重症度、動物の種類および年齢などの任意の数の要因に依存する。
以下の研究を設計し、アジュバント1型極性化樹状細胞(「DC1」)ワクチン接種の役割を調査した。
ネオアジュバント療法後に残存疾患を有する4人のHER2+IBC患者は、アジュバントHER2パルスDC1ワクチンを受けた。各患者のTh1免疫応答を、DC1ワクチン接種前、DCワクチン接種3ヶ月後、およびワクチン接種6ヶ月後に決定し、6つのHER2クラスIIペプチド(配列番号1〜6)でパルスした患者PBMCから、上記のようにELISPOTを介してIFNγ産生を測定することにより生成した。自己DC1ワクチンを前述のように調製した。応答は、(1)全体的な抗HER2応答性(≧1のペプチドに応答する)、(2)反応性ペプチドの数(応答レパートリー)、および(3)6つのHER2ペプチドにわたる累積応答で評価した。
応答性:刺激を受けていないバックグラウンドを差し引いた後の実験ウェル中>20SFC/106細胞として定義される免疫応答を、ワクチン接種前には1人のIBC患者しか示さなかった。ワクチン接種前の結果と比較して、全てのワクチン接種を受けたIBC患者は、抗HER2 IFN-γposThl応答における>2倍の増加として定義される免疫応答を示した。
ネオアジュバント化学療法での治療後に残存疾患を有するHER2+IBC患者のHER2パルスDC1ワクチン接種は、抗HER2 Th1免疫応答を高める。
以下の研究を設計し、抗HER2 Th1免疫を回復させる上での養子T細胞移植の役割を調査した。T細胞を、抗原特異性および細胞機能を維持しながら、養子療法およびエピトープマッピング研究に必要なレベルまで増殖させる。
(HER2特異的DC1の調製:)
前述のように、HER2ペプチドパルスDC1ワクチンでワクチン接種されたHER2乳がん患者(DCIS)からDC前駆体を得た。DC前駆体は、タンデム白血球除去療法/向流遠心溶出法によって得た。DCを、3×106細胞で、GM-CSF 50ng/ml(Berlex社、リッチモンド、カリフォルニア州)を有する1mlマクロファージ無血清培地(SFM-Gibco Life Technologies社、カールズバッド、カリフォルニア州)中37℃でインキュベートした。細胞を最初に播種した48〜72時間後に、DCを、単一HER2ペプチド抗原(42-56,98-114,328-345,776-790,927-941,1166-1180(配列番号1〜6));20μg/ml)でパルスした。成熟のために、DCを、6時間後にIFN-γ(1000U/ml)で、次の日にリポ多糖(「LPS」)(10ng/ml)でさらに活性化させた。HER2特異的DC1を、LPS投与の6時間後に、最大のIL-12産生時点で採取した。
リンパ球を、タンデム白血球除去療法/向流遠心溶出法により、事前にワクチン接種(HER2-パルスDC1ワクチン接種)を受けた乳がん患者からも得た。CD4+T細胞は、ヒトCD4+T細胞Enrichment Kit(Stemcell Technologies社;バンクーバーBC、カナダ)を用いる陰性選択により精製した。CD4+T細胞を、2x106細胞/mlで、培養培地(イスコフ培地、1%L-グルタミン、1%ペニシリン/ストレプトマイシン、1%ピルビン酸ナトリウム、1%非必須アミノ酸、Mediatech;マナッサス、バージニア州、および5%熱不活性化ヒトAB血清)中に再懸濁した。
DC1を、CD4+T細胞と共に、1:10の比率(2×105個のDC1/mlと2×106個のCD4+T細胞/ml)で24ウェルプレートに播種し、37℃でインキュベートした。組み換えヒトIL-7(10ng/ml)およびIL-15(10ng/ml)(BioLegend社;サンディエゴ、カリフォルニア州)を、共培養の48〜72時間後に添加した。IL-7およびIL-15を添加してから24時間後に、組み換えヒトIL-2(5U/ml)を添加した。
DCのさらに2つの群を、上記のように調製した。1つの群では、各ウェルを単一ペプチド抗原(20ug/ml)でパルスし、未成熟DC(「iDC」)とみなした。第2群では、各ウェルを単一ペプチド抗原(20μg/ml)でパルスし、上記のようにDC1に成熟させた。前のDC1共培養の7〜9日後に、HER2特異的CD4+T細胞を採取した。ELISA試験用に、T細胞をiDCと共培養した。インターフェロンガンマ産生を、ELISAアッセイによって、製造業者の推奨およびプロトコルに従って測定した。T細胞もDC1と共培養し、上記のようにIL-7/15およびIL-2で刺激した。このサイクルを、CD4+T細胞とHER2特異的DC1との共培養と共に合計4回繰り返した。
前述のように、HER2特異的DC1を開発する
1日目:単球を培養する(各ペプチドの1つのウェル)
4日目:HER2特異的DC1を成熟させる
AM:抗原(20μg/ml)でパルスする。
PM(6時間後):IFN-γを添加する
5日目:CD4+T細胞およびDC1共培養物を精製する。
AM:LPS
6時間後:共培養:2x106個のCD4+T細胞と2x105個のDC1
*共培養の48〜72時間後:IL-7(10ng/ml)およびIL-15(10ng/ml)を添加する
IL-7/15を添加してから24時間後:IL-2(5U/ml)を添加する
(IL-2単独条件では、IL-2を共培養の72〜96時間後に添加した(IL-2がIL2/7/15群に加えられたのと同時に)
ELISA試験用のHER2特異的iDCならびに再刺激用のHER2特異的DC1の両方を作る
9日目〜11日目:単球を培養する(各ペプチドの2つのウェル)
単球を培養してから48時間後:HER2特異的未成熟DCを処理し、DC1を成熟させる
iDC:抗原(20μg/ml)でパルスする(将来のiDCおよびDC1に同時に与えられる)
DC1:AM:抗原(20μg/ml)でパルスする。
PM(6時間後):IFN-gを添加する
翌日:iDC共培養およびDC1共培養(すなわち、DC1共培養の7〜9日後)
DC1:AM:LPS
HER2特異的CD4+T細胞を採取する
HER2特異的iDCを採取する
→共培養:2x106個のCD4+T細胞と2x105個のiDC
HER2特異的DC1を収穫する
→共培養:2x106個のCD4+T細胞と2x105個のDC1
翌日:iDC共培養物にELISAを実行する
上記過程を繰り返す;IL7/15刺激時に再開する(*)
図3〜16に結果を示す実験および研究において、上述の方法を使用した:
IL-2、HL-7、およびIL-15で刺激されたHER2-ペプチドパルスDC1とのCD4+T細胞の反復共培養は、高度に特異的な抗HER2 Th1細胞の有意な増殖をもたらし、養子移植用細胞の潜在的な集団を提供する。
Claims (16)
- 抗原に対するワクチン接種を受けた被験体由来の血液試料から得られた少なくとも1つのT細胞を含むT細胞集団を増殖させる方法であって、前記T細胞を、1つ以上の樹状細胞(「DC」)またはその前駆体と、少なくとも2つのサイトカインと、T細胞増殖因子と接触させる工程を含む方法。
- 前記血液試料が、前記ワクチン抗原に特異的な前記集団の少なくとも1つのT細胞と少なくとも1つのDC前駆体とを含む、請求項1に記載の方法。
- 前記DC前駆体が前記抗原でパルスされ、抗原特異的I型樹状細胞(「DC1」)に活性化され、次いで前記T細胞と共培養されて抗原特異的DC1を生成する、請求項1に記載の方法。
- 少なくとも2つの前記サイトカインが、インターロイキン-7(「IL-7」)とインターロイキン-15(「IL-15」)とを含む、請求項1に記載の方法。
- 前記T細胞増殖因子がインターロイキン-2(「IL-2」)を含む、請求項1に記載の方法。
- 請求項1に記載の方法であって、
a)前記患者試料からの前記T細胞を、前記抗原特異的T細胞自己I型樹状細胞(DC1)とin vitroで共培養する工程と;
b)工程a)からの前記細胞をIL-7およびIL-5と接触させ、刺激された抗原特異的T細胞を生成する工程と;
c)その後、前記の刺激された抗原特異的T細胞をIL-2と接触させ、それによって抗原特異性および細胞機能を維持する増殖した抗原特異的T細胞集団を生成する工程
とをさらに含む方法。 - 工程a)〜c)を1回から少なくとももう3回繰り返し、さらに増殖した抗原特異的T細胞集団を生成する工程をさらに含む、請求項6に記載の方法。
- 前記T細胞がCD4+である、請求項1に記載の方法。
- 前記抗原がHER2である、請求項1に記載の方法。
- HER2に対するワクチン接種を受けた乳がん患者由来の血液試料から得られた少なくとも1つのCD4+T細胞を含むCD4+T細胞集団を増殖させる方法であって、前記CD4+T細胞を、1つ以上の樹状細胞(「DC」)またはその前駆体と、少なくとも2つのサイトカインと、T細胞増殖因子と接触させる工程を含む方法。
- 前記試料中の少なくとも1つのDC前駆体を、少なくとも1つのHER2 MHCクラスIIペプチドでパルスし、前記CD4+T細胞と接触させる、請求項10に記載の方法。
- 少なくとも2つの前記サイトカインが、インターロイキン-7(「IL-7」)とインターロイキン-15(「IL-15」)とを含む、請求項10に記載の方法。
- 前記T細胞増殖因子がインターロイキン-2(「IL-2」)を含む、請求項10に記載の方法。
- 請求項10に記載の方法であって、
a)請求項11からの前記T細胞を前記HER2パルスDC1と共培養する工程と;
b)工程a)からの前記細胞をIL-7およびIL-15と接触させ、刺激された抗原特異的T細胞を生成する工程と;
c)その後、前記の刺激された抗原特異的T細胞をIL-2と接触させ、それによって抗原特異性および細胞機能を維持する増殖した抗原特異的T細胞集団を生成する工程
とを含む方法。 - 工程a)〜c)を1回から少なくとももう3回繰り返し、さらに増殖した抗原特異的T細胞集団を生成する工程をさらに含む、請求項14に記載の方法。
- 請求項10に記載の方法であって、前記試料が、
ペプチド42-56:HLDMLRHLYQGCQVV(配列番号1);
ペプチド98-114:RLRIVRGTQLFEDNYAL(配列番号2);
ペプチド328-345:TQRCEKCSKPCARVCYGL(配列番号3);
ペプチド776-790:GVGSPYVSRLLGICL(配列番号4);
ペプチド927-941:PAREIPDLLEKGERL(配列番号5);および
ペプチド1166-1180:TLERPKTLSPGKNGV(配列番号6);
を含むHER2 MHCクラスIIペプチドでパルスされる方法。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5846538A (en) * | 1993-03-17 | 1998-12-08 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the her-2/neu oncogene is associated |
JP2013502235A (ja) * | 2009-08-24 | 2013-01-24 | ベイラー カレッジ オブ メディスン | 複数の腫瘍抗原または複数のウイルスに対する特異的ctl株の作製[関連出願の相互参照] |
JP2013507986A (ja) * | 2009-10-27 | 2013-03-07 | イミュニカム・エイビイ | 抗原特異的t細胞の増殖のための方法 |
JP2014511704A (ja) * | 2011-04-13 | 2014-05-19 | イミュニカム・エイビイ | T細胞のプライミングのための方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8222033B2 (en) * | 2002-08-12 | 2012-07-17 | Argos Therapeutics, Inc. | CD4+CD25− T cells and Tr1-like regulatory T cells |
DK1692505T3 (da) * | 2003-11-03 | 2013-01-02 | Danisco Us Inc | CD4+- Epitoper fra knoglemorfogenetiske protiner |
WO2006124412A2 (en) * | 2005-05-11 | 2006-11-23 | The Trustees Of The University Of Pennsylvania | Methods for the rapid expansion of antigen specific t-cells |
DK1956080T3 (da) * | 2005-08-08 | 2012-01-23 | San Raffaele Centro Fond | Anvendelse af IL-7 og IL-15 til genmodificering af hukommelses-T-lymfocytter |
US8895017B2 (en) * | 2010-06-07 | 2014-11-25 | Pfizer Inc. | HER-2 peptides and vaccines |
CN102838679B (zh) * | 2011-06-23 | 2017-10-17 | 中国人民解放军第二军医大学 | Her2‑neu抗原阳性肿瘤治疗性疫苗的制备及应用 |
-
2016
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5846538A (en) * | 1993-03-17 | 1998-12-08 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the her-2/neu oncogene is associated |
JP2013502235A (ja) * | 2009-08-24 | 2013-01-24 | ベイラー カレッジ オブ メディスン | 複数の腫瘍抗原または複数のウイルスに対する特異的ctl株の作製[関連出願の相互参照] |
JP2013507986A (ja) * | 2009-10-27 | 2013-03-07 | イミュニカム・エイビイ | 抗原特異的t細胞の増殖のための方法 |
JP2014511704A (ja) * | 2011-04-13 | 2014-05-19 | イミュニカム・エイビイ | T細胞のプライミングのための方法 |
Non-Patent Citations (5)
Title |
---|
CZERNIECKI, B.J., ET AL.: ""Targeting HER2/neu in early breast cancer development using dendritic cells with staged interleukin", CANCER RES., vol. 67, no. 4, JPN6019051682, 15 February 2007 (2007-02-15), pages 1842 - 1852, XP055269484, ISSN: 0004316530, DOI: 10.1158/0008-5472.CAN-06-4038 * |
DISIS, M.L., ET AL.: ""HER-2/NEU VACCINE-PRIMED AUTOLOGOUS T-CELL INFUSIONS FOR THE TREATMENT OF ADVANCED STAGE HER-2/NEU", CANCER IMMUNOL. IMMUNOTHER., vol. 63, no. 2, JPN5018001448, February 2014 (2014-02-01), pages 101 - 109, XP055318669, ISSN: 0004316529, DOI: 10.1007/s00262-013-1489-4 * |
PEREZ, S.A., ET AL.: ""HER-2/neu-derived peptide 884-899 is expressed by human breast, colorectal and pancreatic adenocarc", CANCER IMMUNOL. IMMUNOTHER., vol. 50, JPN6019051677, 2002, pages 615 - 624, XP037120629, ISSN: 0004316527, DOI: 10.1007/s002620100225 * |
SCHLIENGER, K., ET AL.: ""Efficient priming of protein antigen-specific human CD4+ T cells by monocyte-derived dendritic cell", BLOOD, vol. 96, no. 10, JPN6019051684, 15 November 2000 (2000-11-15), pages 3490 - 3498, XP000985928, ISSN: 0004186182 * |
SOTIRIADOU, R., ET AL.: ""Peptide HER2(776-788) represents a naturally processed broad MHC class II-restricted T cell epitope", BRITISH JOURNAL OF CANCER, vol. 85, no. 10, JPN6019051679, 2001, pages 1527 - 1534, XP002400860, ISSN: 0004316528, DOI: 10.1054/bjoc.2001.2089 * |
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