Cancer is more common than you think. It is
the second leading cause of death, after heart disease in the U.S[1],
and a leading cause of death globally.[2]
In developed countries, 40-50% of people will get cancer in their lifetime[3],
and of the 40-50% of people who get cancer, around 50% will be cured.[4]
Traditional treatments for cancer include chemotherapy, surgery, and radiation.[5]
Traditional treatments have several limitations, for instance, surgery and
radiation can only remove or kill cancer cells in localized tumors but cannot
eliminate tumor cells that have left the primary tumor site. Chemotherapy works
by killing rapidly dividing cells, including tumor cells but also healthy cells
that rapidly divide. The limitations of traditional therapies lead to treatment
failures and relapses which cause the majority of cancer-related deaths.
Therefore, there is a need for new therapies for cancer, including immunotherapy
which utilizes the body’s T-cells.
Over the summer, I
did research with the Kohler Lab on a type of cancer immunotherapy treatment called
Chimeric Antigen Receptor (CAR) T-cell. It is a treatment where T-cells from a patient
are genetically modified so they will target cancerous cells through the
recognition of an antigen expressed on the surface of cancer cells by the
Chimeric Antigen Receptor. CAR T-cells have had multiple successes in patients.
Currently, there are six FDA-approved CAR T-cell therapies treatment. Four of
those target CD19 antigens, and two of those target BCMA.[6] However, there are
limitations in CAR T-cell therapies which lead to relapses. Those are short persistence
and decreased sensitivity to low levels of antigens. Those limitations are
predicted to stem from a weakening of LAT signaling, which is an important
molecule in T-cell’s activation mechanism.
To combat these
limitations, the Kohler Lab is researching on Adjunctive LAT-activating CAR T-cell
(ALA-CART). ALA-CART places a LAT CAR next to a standard CAR to force the
interaction between the LAT molecule and the CAR T-cell[7], instead of relying on
endogenous LAT molecules. LAT molecule is an important molecule in T-cell's activation mechanism. So far, ALA-CART has shown promising results, which
enhances antigen sensitivity and persistence of CAR T-cells.[8],[9]
[1]
Centers
for Disease Control and Prevention. An Update on Cancer Deaths in the
United States. Atlanta, GA: US Department of Health and Human
Services, Centers for Disease Control and Prevention, Division of Cancer
Prevention and Control; 2022. https://www.cdc.gov/cancer/dcpc/research/update-on-cancer-deaths/index.htm
[2] World Health Organization. Cancer. Feb 3 2022. https://www.who.int/news-room/fact-sheets/detail/cancer
[3] American Cancer Society. Cancer
Facts & Figures 2022. Atlanta: American Cancer Society; 2022.
[4] American Cancer Society. Cancer
Facts & Figures 2022. Atlanta: American Cancer Society; 2022.
[5] MedlinePlus [Internet]. Gersten, Todd
(MD): National Library of Medicine (US); [updated Oct 28 2021; cited 2023 Jul
16]. Available from: https://medlineplus.gov/ency/patientinstructions/000901.htm#:~:text=If%20you%20have%20cancer%2C%20your,%2C%20hormonal%20therapy%2C%20and%20others.
[6] National Cancer
Institute: “CAR T Cells-Engineering Patients’ Immune Cells to Treat Their
Cancers”. Updated March 10 2022 https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
[7] University of Colorado Cancer Center: Eric Kohler, MD,
PhD, Receives Award to Improve CAR T-cell Therapy”. Feb 24, 2023. https://news.cuanschutz.edu/cancer-center/eric-kohler-ash-scholar-award
[8] Danis,
Catherine, et al. 2023. https://doi.org/10.1158/1538-7445.AM2023-3190
[9] Danis,
Catherine, et al. 2022. https://doi.org/10.1158/1538-7445.AM2022-3607
This is a really interesting topic and a great post, and it is definitely something that would benefit a lot of people if it were to be used, as you said cancer is one of the leading causes of death. One question that came up while reading was if there were any negative effects from the use of CAR T-cell therapy. I did some more research and found that cytokine-release syndrome (CRS) is one of the more serious side affects that is commonly associated with this type of therapy. The cytokines are produced when the CAR T cells are preforming their functions in the body to kill the cancer. There is a wide range of symptoms associated with CRS from mild flulike symptoms to things like tachycardia or organ failure. Overall, it seems that CAR T-Cell therapy has a lot of benefits to helping treat cancer, but there are still a lot of considerations and side effects to look at before implementing.
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