Cancer immunotherapy has transformed cancer treatment by empowering the immune system to target and eradicate tumor cells. A cornerstone of this therapeutic approach is monoclonal antibodies (mAbs), which have emerged as highly effective tools in cancer therapy. Monoclonal antibodies can precisely target specific cancer antigens, inhibiting tumor progression or enhancing immune responses against the tumor. Developing and optimizing these antibodies require a deep understanding of their molecular structures and functionalities, which is where antibody sequencing becomes crucial.

Antibody sequencing provides insights into the exact amino acid sequences of antibodies, facilitating antibody discovery, engineering, and refinement, especially for cancer immunotherapy. In this blog, we will explore how antibody sequencing contributes to cancer immunotherapy and supports the development of highly effective cancer treatments.

1. Antibody Discovery and Development

In the initial stages of antibody-based cancer therapies, identifying and developing the best candidate antibodies is essential. Monoclonal antibodies are engineered to target cancer cell-specific antigens, but finding the most effective antibody requires rigorous discovery efforts.

Antibody sequencing plays a critical role in this phase by allowing researchers to:

• Identify promising antibody candidates: By sequencing antibodies, scientists can reveal their amino acid sequences and assess how well they bind to cancer antigens [1].
• Optimize antibody specificity and binding: Sequencing helps identify which variants of an antibody offer the highest specificity and affinity to the target cancer antigen [2].

The precise data provided by antibody sequencing accelerates antibody discovery efforts, making it easier to develop effective therapeutic candidates that target tumors with greater efficiency.

2. Humanization of Antibodies

Many monoclonal antibodies used in cancer therapy are originally derived from non-human species, such as mice. While these antibodies may be effective, they often trigger immune responses when administered to humans. To prevent this, these antibodies undergo humanization, a process in which the antibody structure is altered to reduce its immunogenicity.

Antibody sequencing is indispensable in this process because:

• It identifies the original structure: By sequencing the murine or non-human antibody, researchers can determine the regions responsible for immune reactivity and those essential for antigen recognition [3].
• It guides the design of humanized antibodies: With detailed sequence data, scientists can replace the non-human regions with human equivalents, ensuring that the therapeutic antibody retains its function while minimizing immune system rejection [4].

The humanization process ensures that therapeutic antibodies are well-tolerated in patients, enhancing the safety and efficacy of cancer immunotherapy.

3. Affinity Maturation and Enhancing Efficacy

The efficacy of monoclonal antibodies in cancer immunotherapy depends largely on their ability to bind strongly to their target antigen. Affinity maturation is a technique used to enhance this binding capability, improving the antibody’s overall therapeutic potential. Through sequencing, scientists can:

• Track and select beneficial mutations: Sequencing enables the identification of mutations in antibody variable regions, which can enhance binding affinity [5].
• Rationally design higher-affinity antibodies: By analyzing sequencing data, researchers can modify the antibody’s sequence in a way that enhances its ability to recognize and bind to cancer cell antigens [6].

As a result, antibody sequencing helps improve the potency of therapeutic antibodies, ensuring better patient outcomes in cancer immunotherapy.

4. Personalized Cancer Immunotherapy

Personalized cancer treatment tailors therapies to the specific biological makeup of a patient’s tumor. This approach has gained significant traction in the oncology field, and antibody sequencing plays a central role in enabling personalized therapies.

Antibody sequencing allows:

• Identification of patient-specific antibodies: Sequencing the antibodies naturally produced by a patient’s immune system helps identify those uniquely suited to target the cancer cells present in the body [7].
• Monitoring the immune response: Sequencing can track how a patient’s immune system responds to therapeutic antibodies, helping clinicians make informed decisions about adjusting treatment strategies [8].

Personalized immunotherapy has the potential to improve efficacy and minimize side effects, making antibody sequencing indispensable in developing tailored cancer therapies.

5. Overcoming Resistance in Immunotherapy

Cancer cells can develop resistance to therapies, which is a significant obstacle in cancer treatment. Tumors may evolve mechanisms to evade recognition by monoclonal antibodies or other immune responses. Antibody sequencing can assist in overcoming these challenges by:

• Identifying resistance mechanisms: Sequencing can reveal mutations in cancer cells that allow them to escape immune detection. This enables researchers to modify or design new antibodies that circumvent these resistance mechanisms [9].
• Designing new antibody variants: Sequencing allows researchers to adapt existing therapeutic antibodies to target newly emerged mutations in tumor antigens [10].

By addressing these resistance issues, antibody sequencing ensures that cancer immunotherapies remain effective even in difficult-to-treat cases.

6. Supporting Bispecific and Multispecific Antibody Development

Bispecific and multispecific antibodies, which target more than one antigen simultaneously, have become an exciting new avenue in cancer immunotherapy. These complex antibodies can simultaneously engage multiple targets, enhancing therapeutic efficacy.

Antibody sequencing supports the development of these advanced antibodies by:

• Guiding the creation of bispecific or multispecific constructs: Sequencing data helps ensure that the binding domains of these complex molecules are properly arranged and functional [11].
• Ensuring stability and function: Sequencing allows researchers to analyze and optimize the structure of these antibodies to enhance their stability and therapeutic efficacy [12].

With antibody sequencing, scientists can push the boundaries of immunotherapy by designing more sophisticated and effective antibodies to treat cancer.

Conclusion

Antibody sequencing has become a cornerstone in the development of cancer immunotherapies. From antibody discovery and humanization to enhancing efficacy and supporting personalized therapies, antibody sequencing is integral to the success of these treatments. Furthermore, as cancer cells evolve and develop resistance, sequencing offers solutions to stay ahead of these challenges by adapting therapeutic strategies. As immunotherapies continue to advance, the role of antibody sequencing will only become more significant, offering new hope in the fight against cancer.

For biopharmaceutical companies and research institutions working on cancer immunotherapy, antibody sequencing offers a path to innovation and treatment optimization. By embracing this technology, the development of next-generation cancer therapies becomes more efficient and effective, bringing us closer to a future where cancer is a manageable, if not curable, disease.

At ResolveMass Laboratories Inc., we specialize in cutting-edge antibody sequencing services designed to support cancer immunotherapy developers at every stage. Whether you’re in the discovery phase or working on optimizing therapeutic antibodies, our experienced team is committed to helping you achieve your goals.

Contact us today to learn how our antibody sequencing services can enhance your cancer immunotherapy research and accelerate the development of life-saving treatments.

References

1. Grilo, A. L., & Mantalaris, A. (2019). The Increasingly Human and Profitable Monoclonal Antibody Market. Trends in Biotechnology, 37(1), 9-16. DOI: 10.1016/j.tibtech.2018.05.014
2. Zahavi, D., & Weiner, L. M. (2020). Monoclonal Antibodies in Cancer Therapy. Antibodies, 9(3), 34. DOI: 10.3390/antib9030034
3. Jefferis, R. (2016). Humanization of Antibodies for Therapy. Expert Opinion on Biological Therapy, 7(5), 801-813. DOI: 10.1517/14712598.7.5.801
4. Kaplon, H., Reichert, J. M. (2019). Antibodies to Watch in 2019. mAbs, 11(2), 219-238. DOI: 10.1080/19420862.2018.1556465
5. Koenig, P., et al. (2018). Structure-Guided Multispecific Antibody Design. Nature Structural & Molecular Biology, 25, 677-684. DOI: 10.1038/s41594-018-0089-9
6. Adair, J. R., et al. (2018). Engineering Antibodies for Cancer Therapy. Immunotherapy, 10(4), 349-361. DOI: 10.2217/imt-2017-0131
7. Chan, A. C., & Carter, P. J. (2010). Therapeutic Antibodies for Autoimmunity and Inflammation. Nature Reviews Immunology, 10(5), 301-316. DOI: 10.1038/nri2761
8. Vacchelli, E., et al. (2015). Trial Watch: Monoclonal Antibodies in Cancer Therapy. OncoImmunology, 4(4), e1008814. DOI: 10.1080/2162402X.2015.1008814
9. Allard, B., et al. (2016). Targeting the CD73–Adenosine Axis in Immuno-oncology. Immunological Reviews, 276(1), 121-144. DOI: 10.1111/imr.12402