Cancer is a deadly disease, characterized by an uncontrolled growth and division of abnormal cells in the body. The very term instills fear in the minds of many, especially in late-stage cancers. 3rd and 4th stage cancers often have a low chance of recovery and a high chance of remission.
Commonly used forms of treatment for late-stage cancer include chemotherapy, targeted therapy, hormonal therapy (for some cancers), and immunotherapy. Among these, immunotherapy has gained a lot of attention in the recent past, especially because of CAR-T therapy. Immunotherapy, in simple terms, wakes up the body’s immune system and prompts it to fight against dangerous cancer cells. The prime component of the immune system which does this is T cells. Ever since a lot of research has been underway about the use of T cells in cancer treatment.
Tumour- Infiltrating Lymphocyte therapy:
A Team led by Dolton came up with a novel tumor-infiltrating lymphocyte therapy (TIL). It is a form of immunotherapy where T cells could target solid tumours and attack them. Combinatorial peptide libraries and proteomic databases identified the antigen specificities of T cell receptors (TCRs). This a technique used on stage 4 melanoma. TCR has a shared recognition motif consisting of three antigen recognition sites. This multi-epitope targeting is what allows a T cell to attack several solid tumours in many ways. These T cells with multi prongs were superior compared to the conventional T cells (which had a single antigen recognition receptor). The key feature of the multi-prong T cell is a Human Leukocyte Antigen (HLA) called MR1. This was a promising candidate for the treatment of cancer.
This is one of the biggest developments in cancer history over the last 50 years.
The most surprising aspect of this treatment is the fact that a single T cell could attack multiple cancers. They could do this by simultaneously recognizing multiple cancer-related proteins. What is even more surprising is the fact that the T cells could distinguish between healthy and tumour cells even 10 years after the TIL treatment.
TIL methodology:
TIL involves taking the patient’s white blood cells from their tumour and culturing them, thereby enabling them to attack their cancer cells better.
This sounds great! But, how does this work?
Despite its 80% success rate during the clinical trials, it was still unknown how this therapy works at a cellular and molecular level. Researchers at Cardiff University, UK attempted to find this out.
Work at Cardiff:
While on their quest to find out how the TIL therapy works, researchers were studied the data from phase 1 and phase 2 clinical trials. 31 melanoma patients who had received TIL therapy still had a strong immune T cell response even a year after their treatment. They were large in number and multi-pronged, indicating this could identify not just melanoma, but different types of cancer . What makes it interesting is that these multi-pronged T cells are only seen in cancer survivors. If this is indeed successful, one could engineer the multi-pronged T cells and use them for treatment regimes similar to engineered CAR-T cells for leukemia. The US Food and Drug Administration approves CAR-T therapy. They differ from the TIL as they involve the reprogramming of certain T cells to target specific cancer-related proteins.
Clinical significance of TIL
What makes TIL very effective is the fact that they originate directly from a solid tumour and are hence more diverse in their attack mechanisms. The use of lab-grown multi-pronged T cells is known to have boosted the patient’s immune system and thereby assisted in killing the cancer cell. Researchers tested the T cells on a wide range of cancer cells, including skin, blood, bone, lung, kidney, breast, prostate, ovarian, kidney, and cervical cancer cells, and the multi-pronged T cells efficiently killed all types of cancer cells.
The above studies were also done in-vivo by injecting T cells (which could recognize MR1) into mice with human cancer and the human immune system. The cancer-clearing effects of this experiment proved encouraging. Furthermore, in addition to distinguishing healthy and cancer cells, the T cells could also destroy the cancer cells of other patients in the laboratory (irrespective of the HLA type).
What’s next?
According to Prof. Andrew Sewell, the lead researcher of this study, plans for future studies in this field are underway. They had to adress the following questions
- The molecular mechanism of MHR1 and what makes it distinguish healthy and cancer cells.
- Clinical trials (human studies) and safety testing.
Lab-grown multi-pronged T cells seem like a strong and effective cancer treatment, especially for late-stage cancers. However, an important point to note is the number of clinical trial patients. A small group of patients participated in the clinical trial and the same must be done on a larger group of patients in order to validate their theory. Although this research is at a basic stage, it has enormous potential if successful.
The research was published in the journal Cell.
What do you think about this discovery on one-size-fits-all cancer treatment? Comment down below.