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Neoantigen T Cell Therapy with Neoantigen Vaccination as a Combination Immunotherapy Against Cancer

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The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a combination immunotherapy approach of neoantigen-specific T cells administered alongside a vaccine targeting the same neoantigen for the treatment of cancer. This approach has been shown to have synergistic effect compared to the vaccine and/or T cell therapy approach alone.
NIH Reference Number
Product Type
  • Adoptive Cell Transfer, ACT, T-Cell Receptor, TCR, Vaccine, Neoantigen, Immunotherapy, Krishna, Rosenberg
Collaboration Opportunity
This invention is available for licensing and co-development.
Description of Technology

Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes autologous, antitumor T cells to attack tumors through recognition of tumor-specific mutations, or neoantigens. A major hurdle in the development of ACT is the exhausted phenotype exhibited by many neoantigen-specific T cells, which limits their efficacy and prevents a sustained immune response. 
Researchers at the National Cancer Institute (NCI) have developed a combination immunotherapy to rescue the function of exhausted, neoantigen-specific T cells and, thus, enhance ACT. The method involves concurrent administration of neoantigen-specific T cells alongside a vaccine targeting the same neoantigens. The antitumor effect of this combination immunotherapy is superior to that mediated by the vaccine or by ACT alone, as measured in vivo by overall survival and tumor regression. Patient T cells genetically engineered with a neoantigen-specific T-cell receptor (TCR) can also be synergistically enhanced when used alongside a vaccine targeting the same antigen in this combination immunotherapy. This combined immunotherapy approach has broad therapeutic potential in a wide range of metastatic cancers, particularly those that are not responsive to traditional treatment methods.
The NCI seeks parties interested in research co-development and/or licensing of this combination immunotherapy approach of neoantigen-specific T cells administered alongside a neoantigen-targeting vaccine to enhance ACT and treat cancer.

Potential Commercial Applications
  • A variety of human cancers potentially amenable to the synergistic combination therapy of adoptive cell therapy (ACT) and tumor vaccine to treat 
  • Cell therapies for which the ACT component can employ isolated exhausted, neoantigen-specific T cells or T cells transduced with a neoantigen-specific TCR 


Competitive Advantages
  • Synergistic, instead of additive, effect observed with this combination therapy based on available in vivo data
  • Increased efficacy of exhausted, neoantigen-specific T cells
  • Reduced toxicity compared to non-tumor specific immunotherapies 
  • T cells and vaccine can target either patient-specific somatic mutations or common driver mutations
  • Broad clinical applications, including solid tumors (which traditional ACT methods have struggled to effectively treat) 



Sri Krishna PhD (NCI), Zhiya Yu Ph.D (NCI), Ken-ichi Hanada MD, PhD (NCI), Steven Rosenberg PhD (NCI)

Development Stage
Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 63/295,762, Filed 31 Dec 2021
Therapeutic Area
Wednesday, August 17, 2022