Gene Therapies Target an Over $100 Billion Cancer Treatment Market

Gene Therapies Target an Over $100 Billion Cancer Treatment Market

Modern medicine’s more than century-long fight to treat cancer and eradicate tumors will likely benefit from a more diverse and effective arsenal in the coming years. Through a variety of routes and techniques, gene therapies are able to deliver genetic material to a specific cell population or tumor that will result in the destruction of the tumor. Gene therapies have already found clinical successes in the treatment of several non-cancer diseases, though the oncolytic or immune system-assisted destruction of tumors relies on specific mechanisms not necessarily transferrable from other gene therapies. In Personalized Gene Therapy for Cancer, Kalorama Information provides a comprehensive look at the nascent market for gene therapies in cancer treatment. The following is a partial review of prospective clinical gene therapies for cancer that are in Phase III trials.

Traditional cancer therapies are limited in effectiveness due to gradually acquired resistance by cancer cells, the localization of therapy, or inability to comprehensively target all cancer cells. Gene therapies for cancer are ideal and potentially much more effective for certain cancer types when using a targeted approach (cancer cell specificity) and recruiting the patient’s own immune system. Advanced forms of cancer are able to progress due to the immune system’s inability to recognize the threat. Gene therapies for cancer that have progressed through clinical trials predominantly use a two-pronged approach in attacking cancer: the use of oncolytic agents (engineered viruses) and the introduction of genetic material that enables immune system recognition of tumor cells.

Advantagene’s Gene Mediated Cytotoxic Immunotherapy (GMCI) gene therapy technique is featured in the Phase III study begun 2011 for newly diagnosed prostate cancer. The GMCI ProstAtak therapy uses an adenovirus vector to deliver (mediate) the delivery of a herpes simplex virus thymidine kinase (tk) gene to tumor cells at the site of the injection. The tk gene works as a ‘suicide gene’ that allows for the enzymatic conversion of a non-toxic, antiviral drug Valacyclovir into a cytotoxic drug that causes tumor cell death during radiotherapy. Tumor cell death causes the release of various antigens including tumor-associated antigens (TAAs), tumor-specific antigens (TSAs) and the vectored tk gene. The various antigens are taken by antigen-presenting cells (APCs) or immune cells that train T-cells to mount a polyvalent immune response against the tumor-associated antigens. The immune response stimulated by GMCI is the major improvement over alternative cancer therapies as it exposes TAAs/TSAs, presents them effectively to the immune system, and significantly increases the number of tumor-specific T-cells.

VBL Therapeutics plans to begin Phase III trials for its VB-111 lead product for the treatment of recurrent glioblastoma multiforme in mid-2015. The gene therapy targets a highly malignant type of brain tumor that generates vasculature tissue in a process known as angiogenesis. Angiogenic tumors are the target of VBL’s Vascular Targeting System (VTS). The VTS technique uses an adenovirus vector containing two sequences - a promoter and anti-tumor sequence. The promoter gene ensures targeted expression of the vector anti-tumor gene only in tumor vessel endothelium. The vector anti-tumor gene causes cell death of the tumor vasculature, cutting blood flow to the solid tumor and leading to significant tumor reduction. VB-111 is intended for combination with chemotherapy and radiotherapy.

Although failing to extend metastatic melanoma patients lives by a statistically significant rate, Amgen demonstrated in its recent Phase III trial that its talimogene laherparepvec (T-Vec) gene therapy resulted in tumor shrinkage and remission. The T-Vec therapy uses modified herpes simplex viruses that selectively induce apoptosis or cell death in tumor cells and cause the tumor cells to secrete GM-CSF responsible for stimulating a strong polyvalent immune response. Amgen is seeking to improve its T-Vec therapy in clinical trials for melanoma by pairing it with oncology drugs.

Cold Genesys is advancing to Phase III trials for its adenovirus-mediated oncolytic gene therapy targeting invasive bladder cancer. Similar to T-Vec, Cold Genesys’ CG0070 modified virus contains a cancer-specific promoter sequence and GM-CSF-encoding sequence that serves to selectively lyse cancer cells and release GM-CSF antigen to train the immune system. Cold Genesys underwent a round of financing in mid-2014 with the goal of funding CG0070’s Phase III trials.

BioCancell is also developing a bladder cancer gene therapy, BC-819, that uses a DNA plasmid as an alternative to a viral vector. The plasmid contains a cancer-specific promoter sequence and diphtheria toxin ‘A’ (DTA) sequence that causes cytotoxicity and cell death only among cancer cells. BioCancell is commencing Phase III trials for BC-819 in 2015.

Kalorama Information’s In Personalized Gene Therapy for Cancer reviews the many more gene therapies for cancer that are in development, including Phase I and II trials. The report also explores the future market for gene therapies in cancer treatment and identifies the most appealing applications of gene therapy by cancer type.