DK2831109T3 - Kombinatorisk gamma-9-delta-2-t-celle-receptor-kædeudveksling - Google Patents

Kombinatorisk gamma-9-delta-2-t-celle-receptor-kædeudveksling Download PDF

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DK2831109T3
DK2831109T3 DK13716461.2T DK13716461T DK2831109T3 DK 2831109 T3 DK2831109 T3 DK 2831109T3 DK 13716461 T DK13716461 T DK 13716461T DK 2831109 T3 DK2831109 T3 DK 2831109T3
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acid sequence
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Juergen Herbert Ernst Kuball
Elsa Cordula Gruender
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Gadeta B V
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Claims (13)

1. Y952T-celle-receptor, eller et fragment deraf, hvor receptoren eller fragmentet deraf kan binde til en tumorcelle, og hvor receptoren omfatter en y9-T-celle-receptorkæde, der omfatter en Y9-CDR3-region, hvor aminosyrese-kvensen af y9-CDR3-regionen, der svarer til aminosyrerest 122-124 af SEQ ID N0.1, er modificeret, og en 52-T-celle-receptorkæde, der omfatter en 52-CDR3-region, hvor aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 115-122 af SEQ ID N0.2, er modificeret, hvor kombinationerne af aminosyremodifikationerne i y952T-celle-receptoren, eller et fragment deraf, er som anført i tabel 1.
2. y952T-celle-receptor, eller et fragment deraf, hvor receptoren eller fragmentet deraf kan binde til en tumorcelle, og hvor receptoren omfatter: en y9-T-celle-receptorkæde, der omfatter en y9-CDR3-region, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 122-124 af aminosyresekvensen med SEQ ID N0.1, er AQQ, og en 52-T-celle-receptorkæde, der omfatter en 52-CDR3-region, hvor aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 115-122 af aminosyresekvensen med SEQ ID NO.2, er ALKRTD.
3. y952T-celle-receptor, eller et fragment deraf, hvor receptoren eller fragmentet deraf kan binde til en tumorcelle, og hvor receptoren omfatter: en y9-T-celle-receptorkæde, der omfatter en y9-CDR3-region, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 122-124 af aminosyresekvensen med SEQ ID N0.1, er IQ, og en 52-T-celle-receptorkæde, der omfatter en 52-CDR3-region, hvor aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 115-122 af aminosyresekvensen med SEQ ID NO.2, er ALKRTD.
4. y952T-celle-receptor, eller et fragment deraf, hvor receptoren eller fragmentet deraf kan binde til en tumorcelle, og hvor receptoren omfatter: en y9-T-celle-receptorkæde, der omfatter en y9-CDR3-region, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 122-124 af aminosyresekvensen med SEQ ID N0.1, er IQ, og en 52-T-celle-receptorkæde, der omfatter en 52-CDR3-region, hvor aminosyresekvensen af 52-CDR3- regionen, der svarer til aminosyrerest 115-122 af aminosyresekvensen med SEQ ID NO.2, er TLGMGGEY.
5. y952T-celle-receptor, eller et fragment deraf, hvor receptoren eller fragmentet deraf kan binde til en tumorcelle, og hvor receptoren omfatter: en y9-T-celle-receptorkæde, der omfatter en y9-CDR3-region, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 122-124 af aminosyresekvensen med SEQ ID NO.1, er AQQ, og en 52-T-celle-receptorkæde, der omfatter en 52-CDR3-region, hvor aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 115-122 af aminosyresekvensen med SEQ ID NO.2, er LLGY.
6. y952T-celle-receptor eller et fragment deraf ifølge et hvilket som helst af kravene 1-5, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 118-121 af aminosyresekvensen med SEQ ID NO.1 er ALWE, og hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 125-132 af aminosyresekvensen med SEQ ID NO.1, er ELGKKIKV, og hvor aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 112-114 af aminosyresekvensen med SEQ ID NO.2., er ACD, og hvor aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 123-127 af aminosyresekvensen med SEQ ID NO.2, er TDKLI.
7. y952T-celle-receptor, eller et fragment deraf, ifølge et hvilket som helst af kravene 1-6, hvor y9-T-celle-receptorkæden omfatter en aminosyresekvens med mindst 60 % sekvensidentitet med aminosyresekvensen med SEQ ID NO.1, og hvor 52-T-celle-receptorkæden omfatter en aminosyresekvens med mindst 60 % sekvensidentitet med aminosyresekvensen med SEQ ID NO.2, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest nummer 122-124 af SEQ ID NO:1, og aminosyresekvensen af 52-CDR3-regionen, der svarer til aminosyrerest 115-122 af SEQ ID NO:2, er i overensstemmelse med tabel 1, og/eller y9-T-celle-receptorkæden omfatter en aminosyresekvens omfattende aminosyrerest 1-121 og 125-315 af aminosyresekvensen med SEQ ID NO.1, og hvor de modificerede am i nosy rerester 122-124 er som defineret i et hvilket som helst af kravene 1-6, og hvor 52-T-celle-receptorkæden omfatter en aminosyresekvens omfattende aminosyrerest 1-114 og 123-293 af aminosy- resekvensen med SEQ ID NO.2, og hvor de modificerede aminosyrerester 115-122 er som defineret i et hvilket som helst af kravene 1-6.
8. Isoleret nukleinsyresekvens, der koder for 52-T-celle-receptorkæden, eller fragmentet deraf, som defineret i et hvilket som helst af kravene 1-7, hvor 52-CDR3-regionen, der svarer til aminosyrerest 115-122 af aminosyresekven-sen med SEQ ID NO.2, er substitueret med aminosyrerest ALKRTD eller LLGY, og/eller y9-T-celle-receptorkæden, eller fragmentet deraf, som defineret i et hvilket som helst af kravene 1-7, hvor aminosyresekvensen af y9-CDR3-regionen, der svarer til aminosyrerest 122-124 af aminosyresekvensen med SEQ ID N0.1, er substitueret med aminosyrerest IQ, hvor den isolerede nukleinsyresekvens fortrinsvis er indeholdt i et genkonstrukt og/eller indeholdt i en retrovirusvektor.
9. Isoleret nukleinsyresekvens, der koder for y952T-celle-receptoren, eller fragmentet deraf, som defineret i et hvilket som helst af kravene 1-7, hvor den isolerede nukleinsyresekvens fortrinsvis er indeholdt i et genkonstrukt og/eller indeholdt i en retrovirusvektor.
10. T-celle, der omfatter y952T-celle-receptoren ifølge et hvilket som helst af kravene 1-7, eller en T-celle, der omfatter den isolerede nukleinsyresekvens, genkonstruktet eller retrovirusvektoren som defineret i krav 9.
11. y952T-celle-receptor, eller fragment deraf, ifølge et hvilket som helst af kravene 1-7, til anvendelse som et medikament, hvor medikamentet fortrinsvis er til anvendelse ved behandling af cancer.
12. Isoleret nukleinsyresekvens ifølge krav 9 til anvendelse som et medikament, hvor medikamentet fortrinsvis er til anvendelse ved behandling af cancer.
13. T-celle ifølge krav 10 til anvendelse som et medikament, hvor medikamentet fortrinsvis er til anvendelse ved behandling af cancer.
DK13716461.2T 2012-03-28 2013-03-28 Kombinatorisk gamma-9-delta-2-t-celle-receptor-kædeudveksling DK2831109T3 (da)

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PCT/NL2013/050235 WO2013147606A1 (en) 2012-03-28 2013-03-28 Combinatorial gamma 9 delta 2 t cell receptor chain exchange

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