US 2022/0064257 A1Published application

Specific t cell receptors against epitopes of mutant myd88l265p protein for adoptive t cell therapy

AssigneeCharite-Universitatsmedizin Berlin

InventorsAntonio PEZZUTTO, Özcan CINAR

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Abstract

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a MYD88 L265P peptide of SEQ ID NO: 2 in the context of HLA-B*07:02 having a high avidity to said peptide/HLA complex. The invention also provides corresponding proteins and host cells, preferably, CD8+ T cells, as well as the medical use of such nucleic acids, proteins or host cells, in particular, in the diagnosis, prevention and/or treatment of a MyD88 L265P expressing cancer such as a non-Hodgkin B-cell lymphoma selected from the group comprising diffuse large B-cell lymphoma (DLBCL), e.g., activated B-cell-like DLBCL (ABC-DLBCL) or pCNS DLBCL, cutaneous DLBCL, leg-type DLBCL or testicular DLBCL; lymphoplasmacytic lymphoma (LPL), e.g., Waldenstrom macroglobulinemia (WM); and IgM monoclonal gammopathy (IgM MGUS).

A nucleic acid encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a MYD88 L265P peptide of SEQ ID NO:

2 in the context of HLA-B*07:02,
a) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
13, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
16;
or
b) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
23, and/or wherein the TCR beta chain construct comprises a CDR1 sequence having a sequence identity of at least 90% to SEQ ID NO:
24, a CDR2 sequence having a sequence identity of at least 90% to SEQ ID NO:
25 and a CDR3 sequence of SEQ ID NO:
26;
or
c) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
33, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
36;
or
d) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
43, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
46, or
e) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
93, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
96, or
f) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
103, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
106;
or
g) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
113, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
116;
or
h) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
123, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
126;
or
i) wherein the TCR alpha chain construct comprises a CDR3 sequence of SEQ ID NO:
133, and/or wherein the TCR beta chain construct comprises a CDR3 sequence of SEQ ID NO:
136.

33 more elements

Facts

Application

17/424,541Filed 21 Jan 2020

Priority

EP 19152801.721 Jan 2019

Published

3 Mar 2022

Term ends

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Classification16 codes

C07K 14/7051
Immunoglobulin superfamily: t-cell receptor -CD3 complex
A61K 31/7088
Carbohydrates; Sugars; Derivatives thereof: compounds having three or more nucleosides or nucleotides
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/32
Characterised by the recombinant expression of specific molecules in the cells of the immune system: t-cell receptors [TCR]

Abstract

Claims20