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Cancer immunotherapy has gained a lot of traction in the last few years, as several novel therapeutics have made their way into the clinic. Among these new therapeutics, bispecific antibodies are some of the most unique. Unlike traditional antibodies, which have two arms that bind to the same molecule, bispecific antibodies are able to recognize and bind to two different targets. This approach is useful for the field of medicine because they have the ability to destroy various types of cancer cells with the aid of T cells at extremely low concentrations.
Use of bispecifics for targeting cancer cells as a therapeutic was first shown in 1985 by Staerz and colleagues[a]. The main function of bispecifics is to stimulate the T cells of our body to be more efficient or to block certain factors that help cancer growth. This helps to effectively target more than one type of tumor antigen and has shown to be more advantageous than monoclonal antibodies (mAbs) which lacks specificity.
T cells of our immune system plays an important role in fighting cancer and have great potential in controlling tumor growth. However, it is very difficult to build an immune response that is specific to cancer because of their close resemblance to healthy tissue, which the immune system is trained not to attack. Due to this, and the additional ability of cancer cells to evade the immune system, it has been harder to treat them.
To resolve this limitation, it’s important to understand both how cancer cells evade the immune system and the different factors that play a key role in tumor selectivity. Recently, research has centered on developing ways to minimize the limitations and maximize the potential of the bispecifics to target these cancer cells. Using bispecifics expands the potential tumor antigens that can be targeted and helps to diversify treatment options for solid tumors and other malignancies[b]. The most recent development has been to use BiTE molecules, (Bi-specific T cell Engagers).
BiTE molecules are antibodies which use one arm of the bispecific to bind the target tumor cell and the other to bind to T cells, thereby physically bringing T cells into close proximity to the tumor cells. Once the T cells are close to the tumor, they are able to kill the tumor cells. The use of this technology is known to be very effective to kill the cancer cells, even compared to other targeted therapies. This platform allows for effective tumor lysis in comparison to other bispecifics due to the specificity of the BiTE molecules and the ability to target specific tumor antigens.
Research has also shown that these molecules do have an effect on a heterogenous tumor population as well. This indicates it might prove to be an effective treatment strategy in case of solid tumors and malignancies which tend to have different tumor antigens on their surfaces[c].
To conclude, the ongoing research and data shows immense promise in BiTEs as the upcoming cancer immunotherapy that will be used to better understand these molecules as a treatment option for solid malignancies and the underlying mechanisms by which cancer cells evade the immune system and continue to progress.
Edited by: Sara Musetti
- Bispecific T cell engagers for cancer immunotherapy- Amelia M. Huehls, Tiffany A. Coupet, and Charles L. Sentman 10.1038/icb.2014.93
- Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety- Diego Ellerman https://doi.org/10.1016/j.ymeth.2018.10.026
- Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics-Karie Runcie, Daniel R. Budman, Veena John & Nagashree Seetharamu https://www.ncbi.nlm.nih.gov/pubmed/30249178
- Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing-Sandra L. Ross, Marika Sherman, Patricia L. McElroy, Julie A. Lofgren, Gordon Moody, Patrick A. Baeuerle, Angela Coxon, Tara Arvedson https://doi.org/10.1371/journal.pone.0183390
- Bispecific T-Cell Engaging Antibodies for Cancer Therapy- Patrick A. Baeuerle and Carsten Reinhardt 10.1158/0008-5472.CAN-09-0547