Biological Therapies in the Treatment of Cancer-Update and New Directions

Abstract

Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new therapies that have contributed to the advances in treatment of certain malignancies. Immunotherapy, which has repeatedly proven to be a breakthrough therapy in melanoma, as well as B-ALL therapy with CAR T cells, are of great merit in this progress. These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Work on improving the therapy with oncolytic viruses is also progressing, and efforts are being made to improve the immunogenicity and stability of cancer vaccines. Combining various biological therapies, immunotherapy with oncolytic viruses or cancer vaccines is gaining importance in cancer therapy. New therapeutic targets are intensively sought among neoantigens, which are not immunocompromised, or antigens associated with tumor stroma cells. An example is fibroblast activation protein α (FAPα), the overexpression of which is observed in the case of tumor progression. Universal therapeutic targets are also sought, such as the neurotrophic receptor tyrosine kinase (NTRK) gene fusion, a key genetic driver present in many types of cancer. This review also raises the problem of the tumor microenvironment. Stromal cells can protect tumor cells from chemotherapy and contribute to relapse and progression. This publication also addresses the problem of cancer stem cells resistance to treatment and presents attempts to avoid this phenomenon. This review focuses on the most important strategies used to improve the selectivity of biological therapies.

Keywords: CAR T cells; biological therapy; cancer; cancer microenvironment; cancer vaccines; oncolytic viruses; recombinant antibodies.

Figure 1

Selected recombinant antibodies developed for anti-cancer therapies. BITE—bispecific T-cell engager, DART—Dual affinity retargeting.

Figure 2

Structure of the first, second and third generation chimeric antigen receptors (CAR) constructed from the variable scFv fragment of a monoclonal antibody and from the cytoplasmic CD3ζ fragment of the T lymphocyte receptor (TCR). D 1 and D2—costimulatory domains.

Figure 3

The effects of oncovirus therapy. Oncolytic viruses selectively replicate and lyse cancer cells compared to normal cells which lack these effects.

Figure 4

The diagram shows combining oncolytic virus therapy and immune checkpoint inhibitors. As a result of the action of oncolytic viruses, neoplastic cells are lysed and the immune response is induced, and thanks to the use of checkpoint inhibitors, the immune defense of the organism is strengthened. Ndv—Newcastle disease virus, Ads—Adenovirus, HSV—Herpes simplex virus, MV—Measles virus, VV—Vaccinia virus, H-1PV—H-1 protoparvovirus.

Figure 5

Diagram showing potential therapeutic targets on cancer cells. TSA—Tumor-specific antigen, TSAAs—Tumor Stroma-Associated Antigens, FAPα—Fibroblast activation protein α, MMPs—Matrix metalloproteinases, TEM 8—Tumor endothelial marker 8, PSMA—Prostate-specific membrane antigen, TRK—tyrosine kinase, TAM—Tumor-associated macrophage, CAF—Cancer-associated fibroblast, M2—Macrophage 2, CXCL12—C-X-C motif chemokine 12, CXCR4—chemokine receptor for CXCL12, OSCC—Oral squamous cell carcinoma, CSC-like—Cancer stem-like cell.