Сytotoxic effect of CAR-T cells against modified MCF-7 breast cancer cell line

Document Type : Original article

Authors

1 Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia

2 Institute of Hematology, Almazov National Medical Research Center, 197341 Saint Petersburg, Russia

3 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

Abstract

The most often diagnosed and fatal malignancy in women is breast cancer. The International Agency for Research on Cancer (IARC) estimates that there are 2.26 million new cases of cancer in 2020.  Adoptive cell therapy using T cells with chimeric antigen receptor shows potential for the treatment of solid tumors, such as breast cancer.  In this work the effectiveness of CAR-T cells against monolayer and three-dimensional bioprinted tumor-like structures made of modified MCF-7 breast cancer cells was assessed. The cytokine profile of supernatants after co-cultivation of MCF-7 tumor cell models with CAR-T cells was also measured to reveal the inflammatory background associated with this interaction.

Keywords

References

  1. Houghton SC, Hankinson SE. Cancer progress and priorities: Breast Cancer. Cancer Epidemiol Biomarkers Prev 2021;30:822-844.
  2. Wang YJ, Wang F, Yu LX, Xiang YJ, Zhou F, Huang SY, Zheng C, Fu QY, Li L, Gao DZ, Zhang Q, Ma ZB, Yu ZG, Liu LY. Worldwide review with meta-analysis of women’s awareness about breast cancer. Patient Educ Couns 2022;105:1818-1827.
  3. Luangwattananun P, Junking M, Sujjitjoon J, Wutti-in Y, Poungvarin N, Thuwajit C, Yenchitsomanus PT. Fourth-generation chimeric antigen receptor T cells targeting folate receptor alpha antigen expressed on breast cancer cells for adoptive T cell therapy. Breast Cancer Res Treat 2021;186:25-36.
  4. Morotti M, Albukhari A, Alsaadi A, Artibani M, Brenton JD, Curbishley SM, Dong T, Dustin ML, Hu Z, McGranahan N, Miller ML, Santana-Gonzalez L, Seymour LW, Shi T, Loo PV, Yau C, White H, Wietek N, Church DN, Wedge DC, Ahmed AA. Promises and challenges of adoptive T-cell therapies for solid tumours. Br J Cancer 2021;124:1759-1776.
  5. Dees S, Ganesan R, Singh S, Grewal IS. Emerging CAR-T cell therapy for the treatment of triple-negative breast cancer. Mol Cancer Ther 2020;19:2409-2421.
  6. Caël B, Galaine J, Bardey I, Marton C, Fredon M, Biichle S, Poussard M, Godet Y, Angelot-Delettre F, Barisien C, Bésiers C, Adotevi O, Pouthier F, Garnache-Ottou F, Bole-Richard E. Umbilical cord blood as a source of less differentiated T cells to produce CD123 CAR-T cells. Cancers (Basel) 2022;14:3168.
  7. Titov A, Kaminskiy Y, Ganeeva I, Zmievskaya E, Valiullina A, Rakhmatullina A, Petukhov A, Miftakhova R, Rizvanov A, Bulatov E. Knowns and unknowns about CAR-T cell dysfunction. Cancers (Basel) 2022;14:1078.
  8. Blaeschke F, Stenger D, Kaeuferle T, Willier S, Lotfi R, Kaiser AD, Assenmacher M, Döring M, Feucht J, Feuchtinger T. Induction of a central memory and stem cell memory phenotype in functionally active CD4+ and CD8+ CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19+ acute lymphoblastic leukemia. Cancer Immunol Immunother 2018;67:1053-1066.
  9. Berger C, Sommermeyer D, Hudecek M, Berger M, Balakrishnan A, Paszkiewicz PJ, Kosasih PL, Rader C, Riddell SR. Safety of targeting ROR1 in primates with chimeric antigen receptor–modified T cells. Cancer Immunol Res 2015;3:206-216,.
  10. Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C, Wang E, Douek DC, Price DA, June CH, Marincola FM, Roederer M, Restifo NP. A human memory T cell subset with stem cell–like properties. Nat Med 2011;17, 1290-1297.
  11. Sommermeyer D, Hudecek M, Kosasih PL, Gogishvili T, Maloney DG, Turtle CJ, Riddell, SR. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia 2016;30:492-500.
  12. Thakur A, Scholler J, Schalk DL, June CH, Lum LG. Enhanced cytotoxicity against solid tumors by bispecific antibody-armed CD19 CAR T cells: a proof-of-concept study. J Cancer Res Clin Oncol 2020;146:2007-2016.
  13. Ando Y, Siegler EL, Ta HP, Cinay GE, Zhou H, Gorrell KA, Au H, Jarvis BM, Wang P, Shen K. Evaluating CAR‐T cell therapy in a hypoxic 3D tumor model. Adv Healthc Mater 2019;8:1900001.
  14. Valiullina AKh, Zmievskaya EA, Ganeeva IA, Zhuravleva MN, Garanina EE, Rizvanov AA, Petukhov AV, Bulatov ER. Evaluation of CAR-T cells’ cytotoxicity against modified solid tumor cell lines. Biomedicines 2023;11:626.
  15. Xue Q, Bettini E, Paczkowski P, Ng C, Kaiser A, McConnell T, Kodrasi O, Quigley MF, Heath J, Fan R, Mackay S, Dudley ME, Kassim SH, Zhou J. Single-Cell Multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response. J Immunother Cancer 2017;5:85.

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