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.
- 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)
- 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