Defeating Cancer with Armed Antibodies and Genetically Modified Immune Cells
DOI:
https://doi.org/10.54097/84jqhm90Keywords:
Antibody-Drug Conjugates (ADCs); CAR-T and TCR-T cell therapy; Cancer immunotherapy; Synergistic cancer treatment; Tumor heterogeneity and drug resistance.Abstract
Cancer has been one of the primary causes of lethality worldwide, driving the demand for innovative treatments alongside traditional methods like surgery, chemotherapy and radiotherapy. Advances in immunotherapy, particularly with antibody-drug conjugators (ADCs) and genetically modified immune cells, such as CAR-T and TCR-T cells, are bringing the goal of defeating cancer closer to reality. ADCs enable the precise delivery of cytotoxic drugs to cancer cells while sparing healthy tissue; CAR-T and TCR-T cells are genetically engineered to enhance immune targeting against tumours. However, these therapies still need to overcome challenges, including side effects, production complexity, and high costs. A synergistic approach that combines ADCs with modified immune cells can solve the problem of tumour heterogeneity and drug resistance. This dual-targeting strategy amplifies cancer cell lethality by combining ADC-induced cytotoxicity with a sustained immune response from CAR-T and TCR-T cells. In addition, early clinical trials have demonstrated that this combination therapy, especially in drug-resistant cancers, improves patient survival and reduces recurrence rates. Although synergetic therapy is still facing problems regarding immune-related side effects and accessibility, this integration effectively enhances cancer immunotherapy, which is personalised, long-lasting, and effective.
Downloads
References
[1] Li, J., Zhang, Y., Fu, T., Xing, G., Cai, H., Li, K. Q., & Tong, Y. (2024). Clinical advances and challenges associated with TCR-T cell therapy for cancer treatment. Frontiers in Immunology, 15, 1487782.
[2] Luo, J., & Zhang, X. (2024). Challenges and innovations in CAR-T cell therapy: a comprehensive analysis. Frontiers in Oncology, 14.
[3] Chang, Y., Chang, M., Bao, X., & Dong, C. (2024). Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment. Bioactive Materials, 42, 379-403.
[4] Zhou, Z., Zhang, G., Xu, Y., Yang, S., Wang, J., Li, Z. ... & Lu, Q. (2024). The underlying mechanism of chimeric antigen receptor (CAR)-T cell therapy triggering secondary T-cell cancers: Mystery of the Sphinx? Cancer Letters, 597, 217083.
[5] Abuhelwa, Z., Alloghbi, A., & Nagasaka, M. (2022). A comprehensive review on antibody-drug conjugates (ADCs) in the treatment landscape of non-small cell lung cancer (NSCLC). Cancer Treatment Reviews, 106, 102393.
[6] López de Sá, A., Díaz-Tejeiro, C., Poyatos-Racionero, E., Nieto-Jiménez, C., Paniagua-Herranz, L., Sanvicente, A., & Ocana, A. (2023). Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned. Journal of Hematology & Oncology, 16(1), 118.
[7] Esapa, B., Jiang, J., Cheung, A., Chenoweth, A., Thurston, D. E., & Karagiannis, S. N. (2023). Target antigen attributes and their contributions to clinically approved antibody-drug conjugates (ADCs) in haematopoietic and solid cancers. Cancers, 15(6), 1845.
[8] Marei, H. E., Cenciarelli, C., & Hasan, A. (2022). Potential of antibody–drug conjugates (ADCs) for cancer therapy. Cancer Cell International, 22(1), 255.
[9] Hong, J., Li, K., He, J., & Liang, M. (2024). A New Age of Drug Delivery: A Comparative Perspective of Ferritin–Drug Conjugates (FDCs) and Antibody–Drug Conjugates (ADCs). Bioconjugate Chemistry, 35(8), 1142-1147.
[10] Dri, A., Arpino, G., Bianchini, G., Curigliano, G., Danesi, R., De Laurentiis, M., & Puglisi, F. (2023). Breaking barriers in triple negative breast cancer (TNBC)–Unleashing the power of antibody-drug conjugates (ADCs). Cancer Treatment Reviews, 102672.
[11] Tao, R., Han, X., Bai, X., Yu, J., Ma, Y., Chen, W., & Li, Z. (2024). Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology. Frontiers in Immunology, 15, 1354825.
[12] Cordas dos Santos, D. M., Tix, T., Shouval, R., Gafter-Gvili, A., Alberge, J. B., Cliff, E. R. S., & Rejeski, K. (2024). A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nature medicine, 30(9), 2667-2678.
[13] Uslu, U., Castelli, S., & June, C. H. (2024). CAR T cell combination therapies to treat cancer. Cancer Cell, 42(8), 1319-1325.
[14] Hamilton, M. P., Sugio, T., Noordenbos, T., Shi, S., Bulterys, P. L., Liu, C. L., & Miklos, D. B. (2024). Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy. New England Journal of Medicine, 390(22), 2047-2060.
[15] Ghilardi, G., Fraietta, J. A., Gerson, J. N., Van Deerlin, V. M., Morrissette, J. J., Caponetti, G. C., ... & Ruella, M. (2024). T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy. Nature Medicine, 1-6.
[16] Zhu, W., Zhang, Z., Chen, J., Chen, X., Huang, L., Zhang, X., & Hou, J. (2024). A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma. Signal Transduction and Targeted Therapy, 9(1), 101.
[17] Golikova, E. A., Alshevskaya, A. A., Alrhmoun, S., Sivitskaya, N. A., & Sennikov, S. V. (2024). TCR-T cell therapy: current development approaches, preclinical evaluation, and perspectives on regulatory challenges. Journal of Translational Medicine, 22(1), 897.
[18] Parkhurst, M., Goff, S. L., Lowery, F. J., Beyer, R. K., Halas, H., Robbins, P. F., & Rosenberg, S. A. (2024). Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results. Nature Medicine, 30(9), 2586-2595.
[19] Harrison, C. TCR cell therapies vanquish solid tumors—finally. Nature biotechnology.
[20] Wang, Z., Cho, H., Choyke, P., Levy, D., & Sato, N. (2024). A Mathematical Model of TCR-T Cell Therapy for Cervical Cancer. Bulletin of Mathematical Biology, 86(5), 57.
[21] Maia, A., Tarannum, M., & Romee, R. (2024). Genetic manipulation approaches to enhance the clinical application of NK cell-based immunotherapy. Stem Cells Translational Medicine, 13(3), 230-242.
[22] Švajger, U., & Kamenšek, U. (2024). Interleukins and interferons in mesenchymal stromal stem cell-based gene therapy of cancer. Cytokine & Growth Factor Reviews.
[23] Pan, Y., Wu, X., Liu, L., Zhao, C., Zhang, J., Yang, S., & Rao, L. (2024). Genetically Engineered Cytomembrane Nanovaccines for Cancer Immunotherapy. Advanced Healthcare Materials, 2400068.
[24] Jung, I., Shin, S., Baek, M. C., & Yea, K. (2024). Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications. Experimental & Molecular Medicine, 56(1), 19-31.
[25] Abd El-Hafeez, T., Shams, M. Y., Elshaier, Y. A., Farghaly, H. M., & Hassanien, A. E. (2024). Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs. Scientific Reports, 14(1), 2428.
[26] Looi, C. K., Loo, E. M., Lim, H. C., Chew, Y. L., Chin, K. Y., Cheah, S. C., ... & Mai, C. W. (2024). Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies. Frontiers in Immunology, 15, 1484535.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Highlights in Science, Engineering and Technology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
