Personalized Cellular Immunotherapy for Kidney Cancer
Abstract
There is no efficient therapy for aggressive kidney cancer. About 30% kidney cancer patients do not respond to the most commonly used drug, sunitinib. The remaining 70% of kidney cancer patients respond initially to common drugs but develop resistance to those drugs in 6 to 15 months and die. The inefficiency of these therapies is largely due to the fact that the tumor is heterogeneous in nature; also, the level of tumor antigens expressed in the different stages of cancer varies. Therefore, innovative strategies for the treatment of kidney cancer are urgently needed. Recently, chimeric antigen receptor (CAR) T cell immunotherapy has shown improved antitumor efficacy in some forms of blood cancers. However, the therapeutic potential of CAR T cells in solid tumors, such as kidney cancer, is very limited due to their functional heterogeneity and associated toxicity. In this respect, natural killer T (NKT) cells are more efficient than T cells in cytotoxicity and trafficking to solid tumors. A novel concept of personalized cellular immunotherapy for kidney cancer is proposed here. The idea is to screen biopsy specimens first from individual patients for a panel of known overexpressed tumor antigens and then label two or three of the most abundant antigens with a tag. Once the tumor is marked with the tag, immunotherapy with CAR-NKT cells targeting the tag begins. The engineered NKT cells will recognize and specifically kill kidney cancer cells. Thus, the proposed CAR-NKT is a universal cellular therapy for individualized kidney cancer. The use of CAR-NKT as proposed here for the treatment of kidney is highly innovative in many ways. First, the proposed CAR-NKT cell immunotherapy is the first-ever tool that weaponizes NKT cells to targeted killing of any type of kidney cancer (personalized). The CAR-NKT will also target galectin in the tumor microenvironment promoting the patient s antitumor immune response. Particularly relevant to the US military and Veterans, expression of galectin is increased in the presence of polycyclic aromatic hydrocarbons, common hazardous chemicals associated with war. So, the proposed CAR-NKT is a universal cellular therapy designed to specifically recognize and kill any type of kidney cancer regardless of tumor heterogeneity (personalized based on the abundance of tumor antigens) not only from the civilian population, but also from Veterans and military personnel.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810664
Entities
People
- Hafiz Ahmed
Organizations
- United States Army