Abstract
Infusions with immune cells, such as lymphocytes or natural killer (NK) cells, represent one of several modalities of immunotherapy. In human patients with advanced B-cell leukemia or lymphoma, infusions with chimeric antigen receptor (CAR) T-lymphocytes have shown promising responses. However, the scientific and clinical development of cell-based therapies for dogs, who get cancer of similar types as humans, is lagging behind. One reason is that immune cells and their functionality in dogs are less well characterized, largely due a lack of canine-specific reagents to detect surface markers, and specific cytokines to isolate and expand their immune cells. This review summarizes the current status of canine cancer immunotherapies, with focus on autologous and allogeneic T-lymphocytes, as well as NK cells, and discusses potential initiatives that would allow therapies with canine immune cells to “catch up” with the advances in humans.
Highlights
After many years of trial and error, there is some success to report from human medicine, that the immune system can control, and even reverse, the growth of cancer
Since only a minority of tumor specific antigens have been described in dog tumors, specific and—compared to humans—effective monoclonal antibodies (mAbs), have not been developed, a new mAb against CD20 by Elanco is getting some attention [6]
The company is seeking regulatory approval, which would make it the first approved/commercial cell therapy for dogs. Another type of autologous lymphocyte infusion, which has only been explored in the human setting, so far, utilizes tumor infiltrating lymphocytes (TIL) that are believed to be tumor-specific, as they are isolated from the tumor site, and expanded ex vivo to larger numbers [18]
Summary
After many years of trial and error, there is some success to report from human medicine, that the immune system can control, and even reverse, the growth of cancer. Infusion of autologous T-lymphocytes, engineered to express a chimeric antigen receptor (CAR) for the CD19 B-cell antigen, can induce remissions in patients with advanced lymphoblastic leukemia and lymphoma (reviewed in [2]) Those emerging success stories in human medicine have spurred interest in developing cellular therapies for dogs with cancer [3]. A larger retrospective data analysis confirmed that the relapse rate was lower in dogs who had received an allogeneic transplant from a littermate, compared to the infusion of the dog’s own (autologous) bone marrow stem cells, despite the same doses of chemotherapy and radiation to prepare for the graft This “graft versus leukemia/tumor effect”—as it has become known—is largely mediated through allogeneic activated T-lymphocytes recognizing and responding to antigen differences, thereby attacking any residual cancer cells [9]. A host of immune-suppressive cells, such as myeloid-derived suppressor cells (MDSC) and T-regulatory cells, as well as molecules such as TGF-beta or prostaglandins, can induce fibrosis and affect cytotoxic lymphocyte function [15]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call