CAR-T Cell Therapy

Chimeric Antigen Receptor (CAR)-T cell Therapy is the latest kid in the block of anti-cancer therapy. Everyone talks of it. But the understanding is very limited amongst both medical practitioners and the lay population. Even though this has been touted as a 'living drug' or 'magic bullet', the reality is far from it.

Cytotoxic T cells are the most potent killers of cancer cells. However, these cells are activated and engaged through an intricate and complicated mechanism which involves presentation of the unique proteins of cancer cells through cells which 'professionally' present antigens, such as dendritic cells. This system prevents unchecked activation and potential self-destruction by these potent killer cells.

With the identification of every single human gene and advances in genetic engineering — coupled with the finding of safe ways of carrying out such procedures — the potential cancer protein can now be targeted. We introduce an identifier and engager of the cancer protein, along with a T cell activating gene, in tandem through genetic engineering. These cells can go and directly attack the cancer cell having the designated protein on its surface, without having to go through the natural process of identification, engagement and costimulation. Once the CAR-T cell engages with the protein, the T cell gets activated and kills the cancer cell.

CAR-T cells are specific for 1–2 specific cancer proteins. That particular protein has to be present on all cancer cells but not on normal cells. Such proteins are difficult to identify. Hence, the first attempts at CAR-T cell therapy were carried out targeting cancers of B Lymphocyte origin:

In attempting to target cancers of B cell origin, the normal B cells are also eliminated. However, absence of B cells has been observed in the past not to have acute catastrophic consequences, and replacement immunoglobulin infusions can be used to avoid life-threatening infections. Hence, this group of diseases was targeted initially.

The standard indication is Relapsed or Refractory Disease of any of the above categories.

When the idea of CAR-T cells was conceptualised, there was no premonition about the extent and severity of side effects it might unleash. The following are major side-effects, which can be life-threatening as well:

This is an effective but expensive form of cellular therapy that brings response in refractory B cell malignancies. In some cases of B-ALL, CAR-T cell therapy can even cure the disease with a single therapy. However, in most patients, Allogeneic BMT should be performed to sustain the response and cure the disease. A similar upfront response can be expected in most diseases, but long-term cure remains elusive for most patients.