T cell immune response against a unique antigen signature of malignant cells can be harnessed to mediate regression of a metastatic epithelial cell cancer
Immune system routinely patrols the cells of the body, and upon recognition of a foreign antigen, it will attempt to destroy them. All malignant cells express tumor antigens that the immune system recognizes as non-self, which could potentially trigger an anti-tumor T cell response. Recently, Tran et al., researchers at National Cancer Institute (NCI) made use of patients’ own immune system to attack tumor cells. Their success can be potentially explored to target unique cancer mutations and develop highly personalized immunotherapies against epithelial cancers, which account for about 90% of cancer deaths in the United States.
Specifically, this study has shown that all malignant tumors have genetic mutations, which may result in mutant proteins that are capable of triggering an anti-tumor immune response.
These mutations can be used as a blueprint to specifically attack mutations, which are unique to a patient’s cancer. The authors had previously reported that mutation-reactive T cells, also called tumor-infiltrating lymphocytes (TILs) frequently infiltrate human melanomas. The unique antigen signature of these cells may play a critical role in the clinical efficacy of adoptive cell therapy (ACT) and other immunotherapies in melanoma. In the current study, Tran et al., enrolled a 43-year-old woman with an advanced and deadly type of gastrointestinal cancer that had spread from her bile duct to liver and lungs, despite chemotherapy. Subsequently, the authors determined whether TILs from patient with metastatic gastrointestinal cancer could recognize patient-specific mutations. They used whole-exomic-sequencing-based approach to identify mutations that patient’s immune cells might recognize and it was noticed that patient’s TILs recognized a mutation in a protein called ERBB2-interacting protein (ERBB2IP). The patient underwent adoptive transfer of 42.4 billion TILs containing CD4+ ERBB2IP mutation- reactive T cells followed by four doses of interleukin (IL)–2 to enhance T cell proliferation and functions.
After receiving ACT, the patient experienced disease stabilization for about 13 months, after which disease progression was observed only in the lungs but not liver. Patient was re-treated with ACT in which 95 percent of the transferred cells were mutation-reactive T cells, and tumor regression was observed. These results provide evidence that a T cell response against a mutant protein can be harnessed to mediate regression of a metastatic epithelial cell cancer.
Clearly, T cell infusion has potential therapeutic use against cancer. HemaCare is a leading provider of blood products from both healthy and patient donors. Try out our purified lymphocytes obtained from peripheral and cord for research applications in your lab.
[1.] P. F. Robbins et al., Nat. Med. 19, 747–752 (2013).
[2.] Eric Tran et al., Science. 344, 641-645 (2014).