November 2025

Monoclonal Antibodies: Harnessing the Immune System to Fight Cancer

Joseph Corsini, Ph.D. and Julie Alessandra, MTE

Monoclonal antibodies are a type of immunotherapy (therapy that utilizes the body’s own immune system) that harnesses one of the most powerful aspects of the adaptive immune system, the antibody molecule. Antibodies are proteins whose cognate genes evolved in the jawed fish some 440 million years ago and were passed down to primates and then to us. Famous for their roles in eliminating pathogens from the body, in the past thirty years biotechnologists have discovered ways to genetically engineer antibody genes to generate monoclonal antibodies that kill cancer cells, which in some cases (melanoma and B cell lymphoma/leukemia) have dramatically improved long-term survival and significantly increased the number of complete remissions. The use of monoclonal antibodies in cancer treatment is hinged on four developments in our understanding of the immune system and of cancer processes. The first is our understanding of antibodies and their genes, and the way that the vast repertoire of binding capacities is produced by B cells during immune responses to pathogens. Second has been the ability to genetically engineer antibody genes into E. coli or Saccharomyces which has allowed us to both humanize and produce unlimited supplies of any given monoclonal antibody. The third is our modern knowledge of cancer genetics and protein profiles which has also informed us about targetable (by antibodies) molecules on cancer cells, including recent discoveries of cancer specific proteins expressed by most cancers (neoantigens). The fourth is our understanding of the fact that most tumors suppress anti-tumor immune responses through a variety of mechanisms including the induction of what is known as the checkpoint blockade. The upshot is that we now have many monoclonal antibodies that are very effective against specific cancers and which overall pose a relatively low risk of adverse effects.

The range of monoclonal antibodies used in cancer therapy today is summarized by Zahavi and Weiner (2020). The first monoclonal antibody used as an anti-cancer agent was rituximab, an anti-CD20 antibody that inactivates B cells. Clinical trials showed efficacy in treating follicular B cell lymphomas, and it is currently a mainstay in treating a variety of B cell lymphomas (Kimby 2005; Pierpont et al 2018). Clinical use of rituximab has expanded to autoimmune disease including rheumatoid arthritis and systemic lupus erythematosus (Cohen and Keystone 2015; Ramos and Isenberg 2015). The next FDA approved cancer monoclonal antibody was trastuzumab, which binds to the HER 2 receptor (human epidermal growth factor receptor) on HER2+ breast cancer cells (see Boekhout et al 2011). Since then, monoclonal antibodies have been developed for many other cancers including melanoma, colorectal carcinoma, neuroblastomas, and at least two types of lung cancer (reviewed in Zahavi and Weiner 2020). These antibodies target a wide array of cancer processes, in some cases providing the opportunity for multi-pronged treatments that reduce the development of resistance (Jin et al 2022).

The successes with monoclonal antibodies have in some cases been stunning. Treatment of patients with early stage Her2+ ductile carcinoma (an aggressive form of breast cancer that often recurs) with trastuzumab in combination with chemotherapy drugs has resulted in a 46% reduction in the risk of recurrence and a 30% reduction in mortality (reviewed in Kreutzfeldt et al 2020; Triantafyllidi and Triantafillidis 2022). One study has even shown that 3-year disease free survival can approach 100% in node free situations (Tolany et al 2013). The situation with melanoma is equally striking. Wolchock et al (2017) achieved unheard of improvements in long term survival using combination checkpoint blockade monoclonal antibodies (ipilimumab, nivolumab, pembrolizumab), and in their discussions echo the fact that 20% of late-stage melanoma patients receiving checkpoint blockade monoclonal antibodies survive out to ten years. Carlino et al (2021) point out that while only a minority of late-stage melanoma patients respond to release of the checkpoint blockade, many of those who do respond (up to 20%) seem to experience complete remission. One monoclonal antibody, the dual specificity (binds two different target molecules) blinatumomab, targets CD3 on T cells and CD19 on B cells and in one study achieved and astonishing 43% complete remission in relapsed and refractory B-cell acute lymphoblastic leukemia (Jin et al 2022).  While not always as dramatic, similar monoclonal antibody success stories exist with other malignancies such as lung cancer and renal carcinoma. Thus, these monoclonal antibodies have transformed a late stage melanoma diagnosis from a death sentence into a potential for a cure with odds that, while low, are still tangible.

Tempering these exciting success stories is the fact that monoclonal antibodies, as with any other intervention (excepting of course natural light, whole food diets, proper hydration, and exercise), there are risks associated with the treatments. An overview of these risks is presented in Zhang et al (2025). Generalized adverse events such as serum sickness (an immune response to the monoclonal antibody) and allergic reactions that lead to anaphylaxis have been reported but are generally rare. More common are reactions that are specific to the physiological mechanism of the monoclonal antibody. For example, the monoclonal antibody cetuximab binds the epidermal growth factor receptor on cancer cells, targeting them for killing through complement and natural killer cell processes. The problem is that this receptor protein is also expressed by a variety of other cells in the body, including cells of the mucosal epithelium – which means they can also be targeted for killing by complement, opsonization, and NK activity (see diagram below). The most serious and frequent reactions occur with the checkpoint blockade inhibitor monoclonal antibodies. Because they short circuit the suppressive controls that prevent the immune system responding to tissues in your own body, there is a significantly increased risk of temporary and even permanent autoimmune conditions. In addition to the potential effects of the monoclonal antibody itself, close attention must be paid to the medication profiles of the patient to anticipate potential adverse interactions between the monoclonal antibody and other medications.

Boekhout, A. H., Beijnen, J. H., & Schellens, J. H. (2011). Trastuzumab. The oncologist, 16(6), 800-810.

Carlino, M. S., Larkin, J., & Long, G. V. (2021). Immune checkpoint inhibitors in melanoma. The Lancet, 398(10304), 1002-1014.

Cohen, M. D., & Keystone, E. (2015). Rituximab for rheumatoid arthritis. Rheumatology and therapy, 2(2), 99-111.

Jin, S., Sun, Y., Liang, X., Gu, X., Ning, J., Xu, Y., ... & Pan, L. (2022). Emerging new therapeutic antibody derivatives for cancer treatment. Signal transduction and targeted therapy, 7(1), 39.

 Kimby, E. (2005). Tolerability and safety of rituximab (MabThera®). Cancer treatment reviews, 31(6), 456-473.

Kreutzfeldt, J., Rozeboom, B., Dey, N., & De, P. (2020). The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies. American journal of cancer research, 10(4), 1045.

Pierpont, T. M., Limper, C. B., & Richards, K. L. (2018). Past, present, and future of rituximab—the world’s first oncology monoclonal antibody therapy. Frontiers in oncology, 8, 163.

Ramos, L., & Isenberg, D. (2015). Rituximab: the lupus journey. Current Treatment Options in Rheumatology, 1(1), 30-41.

Ramos, L., & Isenberg, D. (2015). Rituximab: the lupus journey. Current Treatment Options in Rheumatology, 1(1), 30-41.

Ramos, L., & Isenberg, D. (2015). Rituximab: the lupus journey. Current Treatment Options in Rheumatology, 1(1), 30-41.

Tolaney, S. M., Barry, W. T., Dang, C. T., Yardley, D. A., Moy, B., Marcom, P. K., ... & Winer, E. P. (2013). Abstract S1-04: A phase II study of adjuvant paclitaxel (T) and trastuzumab (H)(APT trial) for node-negative, HER2-positive breast cancer (BC). Cancer Research, 73(24_Supplement), S1-04.

Triantafyllidi, E., & Triantafillidis, J. K. (2022). Systematic review on the use of biosimilars of trastuzumab in HER2+ breast cancer. Biomedicines, 10(8), 2045.

Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Rutkowski, P., Grob, J. J., Cowey, C. L., ... & Larkin, J. (2017). Overall survival with combined nivolumab and ipilimumab in advanced melanoma. New England Journal of Medicine, 377(14), 1345-1356.

Zhang, S., Chen, W., Zhou, J., Liang, Q., Zhang, Y., Su, M., ... & Qu, J. (2025). The Benefits and Safety of Monoclonal Antibodies: Implications for Cancer Immunotherapy. Journal of Inflammation Research, 4335-4357.