Antibody Usage on Cancer Researches

A trial made by Memorial Sloan Kettering Cancer Center in New York, gave very promising results for the mismatch repair-deficient locally advanced rectal cancer for 12 patients. Mismatch repair genes are the genes that corrects the DNA mistakes while DNA is copied in the cell. Rectal cancer occurs when cancer cells develop in the rectum. The mismatch repair-deficient locally advanced rectal cancer occurs when tumor cells occurred with mismatch repair gene deficiency. Mismatch repair gene deficiency creates and accumulate mutations on the cell which lead to cancerous cells.

Classical treatment of the rectal cancer is chemotherapy and radiation followed by resection of the rectum. However, Memorial Sloan Kettering Cancer Center achieved treatment with an antibody named dostarlimab.

In the trial, all 12 patients received the immunotherapy treatment dostarlimab as the first-line treatment for mismatch repair-deficient locally advanced rectal cancer [1]. After six months, all 12 patients saw their colorectal cancer tumors vanished entirely. Dostarlimab is a monoclonal antibody treatment which kickstart the immune system against tumor cells. Antibody treatments works to restart immune system. An antibody works by attaching itself to the surface of the target cell, it serves as a red flag to the immune system, saying “you need to kill this cell”. Cancer cells often escapes from the radar of the immune system. By injecting antibodies special to that cancer type, you can achieve a red flag for the cancer cell and a “wake up call” for the immune system. In this trial, antibody worked as anti-programmed cell death protein -1 (PD-1) antibody. PD-1 is a protein that causes tumor cells to evade from the immune system. Dostarlimab works as removing the PD-1 blockade, thus helping immune system to find tumor cells and destroy them.

Immune checkpoints are the best defense system of tumor cells. Tumor cells trick the T-cells by having PD-L1 receptors on them. PD-L1 bond to PD-1 causes T-cell to leave tumor cells as it is. Having a blockade between PD-L1 and PD-1 allows T-cells to kill tumor cells (Figure 2).

Antibodies used a lot for different treatment kinds. Antibodies treatments works by [2];

· Flagging cancer cells

· Triggering cell-membrane destruction

· Blocking cell growth

· Preventing blood vessel growth

· Blocking immune system inhibitors

· Directly attacking cancer cells

· Delivering radiation treatment

In the trial, patients received the antibody every three weeks for six months to be followed by standard chemoradiation and surgery. Patients who achieved a clinical complete response were eligible for omission of chemoradiation and surgery [1].

Study results were presented as a paper on the National library of Medicine by Cercek et al [3]. Cercek et al. [3] shows the results of treatment with programmed death-1 (PD-1) blockade in the context of metastatic disease. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging. By their words;

“At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported.” [3]

Figure 1. Graphic shows the interaction between a tumor cell and T-cell. PD-1 blockade can be seen on the right [4]

There have been lots of advances on the field of cancer. Rectal cancer is one of the fields. Understanding of one of cancer types, can reveal other treatment for others. This will lead to other researches, treatment about other cancer types.

Figure 2. PD-L1 and PD-1 checkpoint causes T-cells to “know” healthy cells and cells that death time come [5]. Tumor cells escape death by T-cells by having PD-L1 receptors on them.

As our understanding of immune checkpoints and antibodies on the tumor cells increased, more and more techniques can be used for cancer therapies. We can increase our weapon against the cancer cells.

National Cancer Institute state the cancer types that can be treated by immune checkpoint [5];

· Breast cancer

· Bladder cancer

· Cervical cancer

· Colon cancer

· Head and neck cancer

· Hodgkin lymphoma

· Liver cancer

· Lung cancer

· Renal cell cancer

· Skin cancer

· Stomach cancer

· Rectal cancer

· Any solid tumor that is not able to repair errors in its DNA that occur when DNA is copied.

Cancer therapies increased greatly in the recent years with more understanding of cancer cell mechanism. As we increase our understanding, we get more weapons against cancer. In order to gain more weapons against cancer, its mechanism and potential targets must be investigated and more specific drugs must be created according to them. And scientists that works on cancer all around the world, do just that.

References

[1] N. Advocate, “Small study, miraculous results: All 14 patients in remission after clinical drug trial,” 07 07 2022. [Online]. Available: https://www.manisteenews.com/news/article/Small-study-miraculous-results-All-14-patients-17225373.php#taboola-1. [Accessed 10 01 2023].

[2] M. Clinic, “Monoclonal antibody drugs for cancer: How they work,” Mayo Clinic, [Online]. Available: https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808. [Accessed 10 01 2023].

[3] L. M. S. J. W. J. S. J. L.-E. M. E. D. I. S. N. S. M. S. R. S. Z. Y. R. S. J. R. B. A. G. P. M. D. A. S. Cercek A, “PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer,” N Engl J Med, vol. 25, no. 386, pp. 2363–2376, 2022 .

[4] N. Yaghoubi, A. Soltani, K. Ghazvini, S. M. Hassanian and S. I. Hashemy, “PD-1/ PD-L1 blockade as a novel treatment for colorectal cancer,” Biomedicine & Pharmacotherapy, vol. 110, pp. 312–318, 2019.

[5] N. C. Institute, “Immune Checkpoint Inhibitors,” National Cancer Institute, [Online]. Available: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors. [Accessed 06 02 2023].