US 12,171,818 B2
Methods of isolating T cells having antigenic specificity for a cancer-specific mutation
Eric Tran, Portland, OR (US); Yong-Chen Lu, Rockville, MD (US); Paul F. Robbins, Chevy Chase, MD (US); and Steven A. Rosenberg, Potomac, MD (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed by The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed on Mar. 8, 2021, as Appl. No. 17/195,072.
Application 17/195,072 is a continuation of application No. 15/515,055, granted, now 10,973,894, previously published as PCT/US2014/058805, filed on Oct. 2, 2014.
Prior Publication US 2021/0220457 A1, Jul. 22, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); C12N 5/0783 (2010.01); C12Q 1/6886 (2018.01)
CPC A61K 39/0011 (2013.01) [C12N 5/0636 (2013.01); C12Q 1/6886 (2013.01); A61K 2039/5158 (2013.01); C12Q 2600/156 (2013.01)] 20 Claims
 
1. A method of preparing a pharmaceutical composition comprising T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising:
identifying one or more genes in the nucleic acid of tumor cells of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence;
inducing autologous antigen presenting cells (APCs) of the patient to present the mutated amino acid sequence encoded by each of the one or more identified genes;
co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence in one or more co-cultures;
assessing each co-culture for autologous T cells having antigenic specificity for the mutated amino acid sequence presented in the context of an MHC class I molecule of the patient;
assessing each co-culture for autologous T cells having antigenic specificity for the mutated amino acid sequence presented in the context of an MHC class II molecule of the patient;
selecting the autologous T cells having antigenic specificity for a mutated amino acid sequence presented in the context of major histocompatibility complex (MHC) molecule(s) expressed by the patient; and
combining the selected autologous T cells with a pharmaceutically acceptable carrier, thereby providing the pharmaceutical composition.