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183 Cancer-mutation-specific T cells: novel immunotherapy approach for low mutational burden patients
  1. Alfred Slanetz,
  2. Walter Barry,
  3. Benjamin Schwarz,
  4. Farzonai Muzaffar,
  5. Ryan Campbell and
  6. Abenezer Abera
  1. Geneius Biotechnology, Inc., Natick, MA, USA


Background Immune checkpoint inhibitors, such as anti-PD1 antibodies, have revolutionized cancer immunotherapy. Their success demonstrates that a patient’s own T cells recognize and treat cancer. However, anti-PD1 therapy is most effective in the treatment of cancers with high mutational burden, ~5% of all malignancies. Therefore, an alternative strategy is necessary to target cancer with lower mutational burden. Importantly, the efficacy of PD-1 blockade is associated with the recruitment of new T cells from the blood rather than the activation of pre-existing tumor infiltrating lymphocytes (Yost K.E., et al. Nat. Med. 2019).

Methods Our approach is to prime and expand T cells from the blood to cancer-specific mutations ex vivo.

Results We can generate T cell populations reactive to as few as 8 and as many as 40 cancer-specific mutant proteins in a single production run. In vitro, these T cells have mutation-specific cytotoxicity and do not kill the normal cells. These T cells express homing receptors that allow them to infiltrate the tumor and express high levels of TNFaand IFNg, both of which are associated with effective tumor cytotoxicity and pro-inflammatory modification of the tumor microenvironment. The predominant immunophenotype of these cells is consistent with central and effector memory, CD4+ and CD8+ T cells, with almost no regulatory or exhausted T cells.

Conclusions We believe these T cells can be used as a cellular therapy in conjunction with, or as an alternative to, immune checkpoint inhibitors to treat lower mutational burden cancers that comprise most patients’ tumors.

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