Tag Archives: cancer immunotherapy

Treating Cancer with Immunotherapy and Targeted Therapy

The development of new cancer therapies has been proceeding at
an astounding rate. These advancements have led to publishing
a second edition of Treating Cancer with Immunotherapy and
Targeted Therapy two years after the first edition.
A more comprehensive understanding of the process of
metastasis has unfolded, leading to the prospect of developing
drugs targeting metastasis. The role of cancer stem cells in the
process is also discussed.

Many new therapies are discussed. An overall theme appears
to be that they are most effective in combination with other
therapies. Combination therapies have led to a reexamination
and renaissance in the use of cancer vaccines. Advances in
messenger RNA technology have resulted in the development of
highly effective mRNA vaccines.

The uses of oncolytic viruses and bispecific antibodies represent
new approaches to immunotherapy. Applying CRISPR
technology to cancer therapy appears promising but is only in
the very early stages of development. The microbiome has vast
influences on human health, the immune system, and cancer
development, and the microbiome’s composition has shown to
affect the outcome of cancer therapies.

The field of cancer therapy is constantly evolving, and this book
is a concise summary of a vast field.

Updates: Subsequent issues of this newsletter will provide new developments in the fields of cancer immunotherapy and targeted therapy since the publication of the second edition.

Bispecific Antibodies for Cancer Treatment

Bispecific antibodies are bioengineered proteins that can simultaneously bind to two different types of antigen (such as found on cancer cells). Bispecific antibodies appear to be destined to play an important role in immunotherapy-based cancer therapy together with checkpoint inhibitors, CAR-T cell therapy, and other types of immunotherapy. Cancer immunotherapy improves the functioning of the immune system to better seek out and destroy cancer cells. Research has uncovered ways to modify immune cells in ways to improve their functioning.

Bispecific antibodies have an advantage over other immunotherapies since they can bring cancer cells and immune cells in closer proximity, allowing immune cells greater opportunity to kill cancer cells. Bispecific antibodies can bind to antigens that are expressed relatively weakly, making them more toxic to cancer cells than other immunotherapies. Also, bispecific antibodies can be mass produced in advance, while CAR-T cells, for example, must be prepared for each cancer patient.

The basic structure of all antibody molecules consists of four protein chains shaped like a capital letter Y. Two chains are longer and are designated “heavy,” while the other two chains are shorter and designated “light.”  Antigen-binding sites are located on the outward tips of the four protein chains. Different regions of the antibody, designated “Fc” and “Fab,” can also serve as binding sites. These regions have significance in the development of bispecific antibodies.

Public Domain (work of the US Government-May 6, 2007)

The bispecific antibody, blinatumomab, was approved by the FDA in 2017 for the treatment of acute lymphoblastic anemia. Another bispecific antibody, catumaxomab, has orphan drug status from the FDA for gastric and ovarian cancers. However, this drug is no longer produced by the manufacturer. Clinical trials are currently underway, studying over fifty bispecific antibodies for various malignancies.

References

  1. Clift,I, “Bispecific, Multispecific Antibodies Grapple with Cancer,” Genetic Engineering & Biotechnology News. Feb. 7, 2019. https://www.genengnews.com/insights/bispecific-multispecific-antibodies-grapple-with-cancer/
  2. Jenks, Susan. “Bispecific Antibodies in Cancer.” Cancer Therapy Advisor. Aug. 22,2018. https://www.cancertherapyadvisor.com/home/cancer-topics/general-oncology/bispecific-antibodies-in-cancer/
  3. Kaiser, Jocelyn. “Designer antibodies fight cancer by tethering immune cells to tumor cells.” Science. May 28, 2020. https://www.sciencemag.org/news/2020/05/designer-antibodies-fight-cancer-tethering-immune-cells-tumor-cells
  4. Runcie, K., et al. “Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.” Molecular Medicine. (2018) 24:50 https://pubmed.ncbi.nlm.nih.gov/30249178/
  5. “Bispecific monoclonal antibody.” https://en.wikipedia.org/wiki/Bispecific_monoclonal_antibody