Dostarlimab is a monoclonal antibody, a prepared molecule in the lab and sold under the brand name Jemperli. This drug is used for the treatment of rectal and endometrial cancer.
Recently in a clinical trial performed on 14 patients for six months, achieved remission with no trace tumors on medical scans and tests, digital rectal exam or biopsy this drug has shown a 100% success rate in rectal cancer patients. Till now none of the patients have required chemo-radiation or surgery, and no cases of progression or recurrence have occurred during follow-up, which is as long as 25 months in some patients.
Although the number of patients in the clinical trial was quite low in the long run scientists will be targeting this molecule on a large number of patients to see its successful effect on a cure for cancer.
Rectal cancer is also a common type of cancer leading to constipation, diarrhea, and blood in fecal matter. In most cases, it is curable and dated by coloscopy.
This molecule was used for the treatment of rectal as well as endometrial cancer, it (endometrial cancer) is the sixth most common type of cancer occurring in women. This uterine cancer is highly lethal and can spread in the pelvic region and thus become very difficult to treat. This Dostarlimab is a new monoclonal antibody drug (immunotherapeutic) molecule and can stimulate the immune system thereby suppressing the growth of cancer cells.
Dostarlimab in treatment of Endometrial & Rectal Cancer
Uterine cancer commonly occurs in women and leads to bleeding between periods or after menopause. In many cases, doctors also advise (removal of the uterus) hysterectomy. Uterine cancer consists of Endometrial Cancer (cancer affecting the reproductive system of women) and uterine sarcoma (affecting the myometrium layer of the uterus), it usually occurs in rare conditions. The exact reason for the spread and cause of this cancer is not known but the scientist estimates that women having PCOS, age, some genetic factors, and lifestyle is the reason for its cause.
Mechanism of Action of Dostarlimab
Dostarlimab is a programmed cell death receptor-1 (PD-1) blocking antibody molecule. PD-1 receptor is a cell surface receptor that regulates T-cell activation through binding to PD-L1 and PD-L2. PD-1 protein is present on the surface of B-cells and T-cells and it has a role in regulating the immune suppression by downregulating the immune system and promoting self-tolerance by suppressing T-cells’ inflammatory activity. This mechanism helps in preventing autoimmune disease, however, due to the killing of T-cells body is not able to produce antibodies to fight against cancer and leading to its spread.
PD-1 is also called an immune checkpoint inhibitor, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in the lymph nodes and second by reducing apoptosis in regulatory T-cells.
PD-1 inhibitors work by blocking these PD-1 receptors, this blockage of PD-1 receptors activates the immune cells to produce antibodies and fight back against it. These PD-1 receptors belong to the class of immunoglobin family and are expressed in T-cells and pro-B cells.
The binding of PD-L1 and PD-L2 to PD-1 receptors inhibits the T-cell’s activity. So this new drug molecule dostarlimab prevents the interaction between PD-L1, and PD-L2 with the PD-1 molecule inhibiting the immune response and thus showing the antitumor activity.
Medicinal Uses of this Drug
This drug is used in the treatment of advanced endometrial cancer and mismatch repair deficient (dMMR) recurrent. In 2020, the GARNET study announced that dostarlimab was demonstrating the potential to treat a subset of women with recurrent or advanced endometrial cancer. On 17, August 2021, US FDA (Food Drug Administration) approved this drug and has progressed on or following prior treatment and has no other alternative treatment option. Its clinical efficacy was reported in the GARNET trial (NCT02715284), it’s a multi-center, multi-cohort, open-label trial in patients with advanced solid tumors.
Side effects were reported in less than 2% of the patient which included sepsis, acute kidney injury, abdominal pain, and pyrexia, and immune-mediated adverse reaction included pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Surgeries and chemotherapies have several side effects leading to infertility, and bowel and bladder dysfunction. So this immunotherapeutic approach for treating rectal and endometrial cancer is a new approach and in the coming future, this drug may provide significant relief in cancer treatment.
The drug molecule has shown its positive impact, although the number of patients involved in the clinical trial was less. With this positive approach, scientists are planning to perform this trial on a large number of patients. It may still take years for this drug to come into the market. In February 2021 The Committee for Medicinal Products for Human Use and European Medicine Agency adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Jemperli, intended for the treatment of certain types of recurrent or advanced endometrial cancer.