Newly discovered superior T-cells might kill tumors in late-stage cancer patients

“These multipronged T-cells could respond to most types of cancer as cancers only needed to express one of the aberrant targets to be identified as dangerous and killed,” he added.

Discovery of superior T-cells

The new T-cell discovery is a result of decade-long work on TIL (Tumour-infiltrating lymphocyte) therapy, a treatment that is employed to kill solid tumors in late-stage cancer patients by targeting the cancer cells with a large number of lab-grown T-cells.  

During their study, the researchers collected new blood samples and stored tumor cell samples of patients who previously participated in Phase 1 and Phase 2 clinical trials of TIL therapy, and are now free from cancer.

When they introduced the cancer cells of patients in their blood cell samples, they noticed a stronger T-cell activity. They were surprised to see that these T-cells were able to differentiate between healthy cells and cancer cells even after 10 years of the TIL treatment. 

Next, the researchers took the help of some algorithms to find out the cancer proteins that the T-cells targeted during the experiment. This analysis resulted in the discovery of a new type of stronger and superior T-cells.   

“We have seen large numbers of multipronged T-cells in the blood of cancer survivors. To date we have not found such multipronged T-cells in people where cancer progresses. Patient numbers are small so far, but it remains possible that multipronged T-cells might be associated with complete remission – or cancer clearance,” said Sewell. 

Multipronged T-cells have immense potential

During TIL therapy, scientists extract T-cells that have already made their way into the tumor of a patient and then multiply these T-cells outside the human body in a lab. Once they grow a large number of T-cells, they again put them back inside the patient’s body. The new T- cells give a boost to the patient’s immune system and assist it in killing cancer. 

It must be noted that not all patients who underwent TIL therapy survived cancer during the phase I and II trials. However, those who did, it is possible their bodies have developed the multipronged T-cells. 

These newly identified superior T-cells might give rise to effective cancer treatment in the future. Plus, since these cells are grown in a lab, they can be modified and grown in large numbers to work against different types of tumors and cancers. 

However, the current study takes into account only a small number of subjects,  according to the researchers. Therefore, a study involving a large cohort of TIL therapy cancer survivors needs to be conducted to further validate their findings. 

“This research enhances our knowledge of the role of the immune system in cancer, and while more work needs to be done, it is a positive step in the development of immunotherapies to treat cancer in the future," said Sewell.   

The study is published in the journal Cell.

Study Abstract:

The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A*02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such ‘‘multipronged’’ T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.