The French Academy of Medicine recognizes the efficacy of cell-based therapies in the treatment of solid tumors in children and adults and supports the impetus for innovation that their development represents. It draws attention to France’s delays in institutional production, which is the only way to optimize a patient-specific production while remaining financially accessible.
Treatment of solid cancers with cell-based therapies: a hope that is becoming a reality1
Press release from the French Academy of Medicine
The recent diversification of cancer treatment using cell-based immunotherapy approaches has led to significant results against solid tumors. Having become key strategies, these distinct approaches include:
– Injection of tumor-infiltrating T lymphocytes (TILs), cultured ex vivo and then reinjected;
– Injection of T lymphocytes transfected with T cell receptors (TCRs) recognizing tumor antigens in a specific HLA context (TCR-Ts);
– Injection of Chimeric Antigen Receptor T cells (CAR-T) (1).
In metastatic melanoma, injection of TILs achieves durable clinical responses, with an overall response rate of more than 30% and an average overall survival of almost 14 months (2). Toxicity is linked to prior lympho-depletion (3).
Begun in 2006 (4), treatments with TCR-modified T lymphocytes have been carried out in metastatic sarcomas expressing antigens identified as playing a role in tumor development, “cancer/testis antigens”, with tumor regression in 50% of patients with synovial sarcoma. This approach has been extended to myxoid liposarcoma, ovarian cancer and head and neck cancers, with evidence of a specific immune response in these types of cancer. Side effects are frequent (70%) and are linked to cytokine release.
Clinical trials with CAR-T cells in solid cancers are more complex to develop, due to the heterogeneity of tumors, physical and immunological barriers, the tumor microenvironment and the lower specificity of targeted antigens. They have given positive responses against glioblastoma, brainstem glioma, resistant prostate cancer, pancreatic and ovarian cancers, small-cell lung cancer and esophago-gastric adenocarcinomas (5):
These treatments are characterized by the complexity of their manufacturing, involving industrial processes and individual adaptation of each preparation. This results in very high manufacturing costs (up to several hundred thousand euros per treatment, resulting in expenses that are difficult for social security organizations to sustain. This cost inflation will only worsen with the likely development of indications for these treatments.
Experiences abroad have shown that university-based production keeps costs down, through competition with manufacturers. The development of such public production is now essential and is the subject of promising projects.
Given the progress made in cell therapy approaches, the French Academy of Medicine recommends that:
– These treatments should be made available at an affordable price to patients with a solid cancer subject to this therapeutic indication. This requires developing facilities in France to produce advanced therapy drugs (ITDs).
– Given the cost implications, a university-industry partnership model should be developed to produce these drugs, which must be tailored to each patient.
– Clinical trials should be facilitated.
References
– Rosenberg S.A., Lymphocytes as a living drug for cancer, Science, 2024;385(6704):25-26.
– Chesney J., Lewis K.D., Kluger H., et al., Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study, J Immunother Cancer, 2022;10(12): e005755.
– Kwong M.L.M., Yang J.C., Lifileucel: FDA-approved T-cell therapy for melanoma, Oncologist. 2024; 29:648-650.
– Morgan R.A., Dudley M.E., Wunderlich J.R., et al., Cancer regression in patients after transfer of genetically engineered lymphocytes, Science, 2006; 314(5796), 126-129.
– De Pinieux G., Karanian M., Le Loarer F., et al., on behalf of the NetSarc/RePPS/ResSos and French Sarcoma Group-Groupe d’Etude des Tumeurs Osseuses (GSF-GETO) networks, Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network. PLoS One. 2021 ; 16(2) : e0246958.
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PRESS CONTACT: Virginie Gustin +33 (0)6 62 52 43 42 virginie.gustin@academie-medecine.fr ACADÉMIE NATIONALE DE MÉDECINE, 16 rue Bonaparte – 75272 Paris cedex 06 Site : www.academie-medecine.fr / Twitter : @Acadmed
1 Press release from the Academy’s Rapid Communication Platform.
