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Cancer immunotherapy’s importance stems from its unique promise of specifically targeting cancer while minimizing collateral damage. Being non-specific is the glaring lacuna with Radiation therapy – Wikipedia and Chemotherapy – Wikipedia, which have dominated cancer Rx, especially since Nixon declared War on Cancer – Wikipedia in 1971 (1). While surgery is a third approach, it is only quasi-specific in so far as it removes as much of tumor and as little of normal tissue as possible. Working best when tumor’s diagnosed early, it’s invasive and therefore risk-laden and also not feasible for many cancers deemed inoperable such as blood cancers, types of melanoma, brain tumors and advanced metastases.

Exemplifying agents of war by any means, these approaches make rather tenuous distinctions between tumor and normal tissues. Chemotherapy mainly targets the cancer cell’s capacity to rapidly divide or for certain genetic and/or metabolic changes, attributes also shared by normal cells. Thus, with these Rx, the normal and the cancerous overlap to various degrees, i.e., these measures are non-specific and therefore entail considerable collateral damage, hair loss, nausea, vomiting, diarrhea, hematopoietic cell loss and therefore greater susceptibility to infections, to mention just a few. Depending on age, general physiological condition, extent of cancer, often collateral damage from these Rx is more damaging (toxic) than even the tumor itself. Resistance is another problem with chemotherapy since cancer cells often adapt to it by developing genetic alterations.

Radiation and chemotherapy became the standard arsenal in the war on cancer by displacing an earlier approach. Exploring cancer therapy landscape through the lens of metaphors proffers a sense of the wheel coming full circle because interestingly enough, the century prior to the war on cancer was dominated by the Magic bullet (medicine) – Wikipedia metaphor as exemplified by Coley’s toxins – Wikipedia, bacterial components used by William Coley – Wikipedia to drive a ‘fever’ dominated response that would get rid of the tumor, a notion premised on the well-substantiated historical observation that spontaneous tumor remissions frequently accompanied acute febrile infections (2, 3, 4, 5, 6).

Having a similar underlying premise, to harness the body’s own immune response capacity to specifically target and eliminate cancer, cancer immunotherapy of the early 21st century is in a way Coley’s Toxins 2.0 (2). Whether cancer immunotherapy’s promise will ever be fully realized, when, for which cancers better than for others, promising answers to such questions still remain very much up in the air because the first chapter of this story is still being written.

  • Cancer immunotherapy only truly fulfills its mandate if it specifically targets the cancer. Even after years of search, few confirmed tumor-specific targets have been identified (7), the first imperative in triggering a truly tumor-specific immune response.
  • The nuts and bolts of human adaptive immune responses themselves, let alone of tumor-specific immune responses, aren’t yet fully deciphered, at least not to the extent of being able to manipulate them at will and that too with sanguine control and predictability. Thus for example, while antibodies against Immune checkpoint – Wikipedia inhibitors such as PD-1 (Programmed cell death protein 1 – Wikipedia) or PD-L1 (PD-L1 – Wikipedia) are among the most prized magic bullets of the day, they don’t fulfill the promise of specificity since they merely remove the brakes from lymphocytes, all lymphocytes that express PD-1, not just those present within tumors or those that can specifically target them. Thus, such Rx too carry the danger of collateral damage (7, 8).
  • The premise of the Chimeric antigen receptor – Wikipedia T cell immunotherapy approach is to take out the patient’s own T cell – Wikipedia and genetically engineer them to target the tumor. So far such approaches have only worked best against B cell – Wikipedia tumors (8, 9, 10). Such customized approaches would also likely be quite costly. How such costs will be managed and paid for if and when such Rx become mainstream is very much unclear.

Bibliography

1. Hanahan, Douglas. “Rethinking the war on cancer.” The Lancet 383.9916 (2014): 558-563. http://www.amec.eu/images/docume…

2. Tirumalai Kamala’s answer to What is the relationship between tumors and immune tolerance?

3. Cann, SA Hoption, J. P. Van Netten, and C. Van Netten. “Dr William Coley and tumour regression: a place in history or in the future.” Postgraduate medical journal 79.938 (2003): 672-680. https://www.ncbi.nlm.nih.gov/pmc…

4. Cann, SA Hoption, et al. “Spontaneous regression: a hidden treasure buried in time.” Medical hypotheses 58.2 (2002): 115-119.

5. Jessy, Thomas. “Immunity over inability: The spontaneous regression of cancer.” Journal of Natural Science, Biology and Medicine 2.1 (2011): 43. http://www.jnsbm.org/temp/JNatSc…

6. Kienle, Gunver S. “Fever in cancer treatment: Coley’s therapy and epidemiologic observations.” Global advances in Health and Medicine 1.1 (2012): 92-100. http://www.gahmj.com/doi/pdfplus…

7. Tirumalai Kamala’s answer to What are the key immunological markers of successful cancer immunotherapy?

8. Tirumalai Kamala’s answer to Is immunotherapy the closest thing we have to a cure for cancer?

9. Tirumalai Kamala’s answer to Why is CAR T not very effective on solid tumors?

10. Tirumalai Kamala’s answer to Why is chimeric antigen receptor better than just injecting anti-CD19 antibodies?

https://www.quora.com/Why-is-cancer-immunotherapy-important/answer/Tirumalai-Kamala

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