Dostarlimab – the remarkable cancer savior
Whenever we hear the term ‘cancer’, our mind ponders the point that it is untreatable, and usually associated with death. Also, in order to treat a patient with cancer, he must undergo a lot of radiation therapy, chemotherapy, and even surgery. Alternatively, we have another way of treatment called immunotherapy and this blog is about such a way of approach that lead to complete remission of cancer in a small trial group. This was conducted at the Memorial Sloan Kettering (MSK) Cancer Center, New York by Dr. Luis Alberto Diaz.
The participants selected for this trial were those who had rectal cancer, “mismatch repair-deficient” rectal cancer to be specific. Chemotherapy and radiation are not effective for this type of cancer. The trial participants received 500 milligrams of ‘Dostarlimab’ every three weeks for six months. The researchers initially expected that the patients needed to undergo chemo or radiation after the treatment of the drug. But to their surprise, all the patients got cleared of cancers only through drug consumption. None of those patients were spotted with tumors in different medical imaging like MRI, PET, Ct, etc. The team reported that the patients who underwent the treatment were completely cured and didn’t have any further growth of tumors.
The most probable causes of cancer can be categorized into genetic and acquired. Acquired are due to various environmental factors called oncogenes that activate certain genes in human chromosomes called pro oncogenes. Various innate cellular mechanisms keep the oncogenic genes inactive in normal human beings. These oncogenes cause progressive and accumulated changes in various genes and once strong enough they over-ride these mechanisms. Hence the pro oncogenes become activated and these are called oncogenes. Once these oncogenes are activated the cells undergo rapid multiplication, invade the normal structures and organs and cause their destruction by varying mechanisms and ultimately death.
In “mismatch repair-deficient”, the cancer cells initially acquire point mutations in their genome and lack the capacity to effectively correct the mutation. The normal cells, if acquired these mutations, they undergo apoptosis by intrinsic pathway or by death-ligand pathway. These cancer cells escape the mechanism of apoptosis but rather start to proliferate. These cancer cells also express lots of antigens that are necessary to recognize and destroy the immune cells and also a lot of ways to counter these immune cells.
These dead cells simulate local immune tissue-resident cells like the dendritic cells. The dendritic cell then migrates to the regional lymph node and causes activation of cell-mediated immunity called the T lymphocyte. The dendritic cell activates the T killer cells which proliferate in the same regional lymph node and recognize until the metastatic site and kill these cells. The T helper cells are also activated producing a cytokine IFN-gamma that activates macrophages, and phagocytosis of cancer cells occurs.
There are lots of methods of immune evasion, but one of the methods pertaining to this drug includes an immune checkpoint. The cancer cells express surface proteins called PDL-1 that inactivate T killer cells by binding to PD 1(a T killer cell surface protein). The cancer cells also become failed to recognize immune cells by preventing the assembly of surface proteins (MHC class 1) necessary for recognition by T killer cells.
The drugs ‘Dostarlimab’ and ‘Pembrolizumab’ which showed benefits as a first-line treatment in patients with metastatic mismatch repair-deficient cancers’ is a checkpoint inhibitor, which makes it easy for immune recognition. These drugs belong to a drug class known as Monoclonal Antibodies. Pembrolizumab blocks the receptor protein PD 1 in T lymphocytes. But whether this can be employed as a standard treatment still remains a question? Further research is required to use these drugs, as checkpoint inhibitors can last for years, and in general, cancer regrowth occurs in about 20% to 30% of patients. Also very little about the duration of cure using the drug ‘Dostarlimab’ is known.
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