Lymphocytes to the Rescue: Strategies for Using T Cells to Fight Cancer

Biologics

Lymphocytes to fight cancer
With recent advances in cancer immunotherapies, researchers are gaining better insight into how to harness the body’s own immune system to fight off cancer. Image Source: Flickr User NIH Image Gallery

Cancer cells are often present in the body without ever turning into full-blown cancer. In theory, the body has natural mechanisms which seek out and destroy cancer cells. It truly becomes “cancer” when cancer cells are able to evade immune detection and destruction, and set up camp within the body. Last winter, researchers saw unprecedented success in treating cancer using a new T cell therapy technique. Generally, T cells are unable to respond quickly or aggressively enough to deter fast growing tumors. Dr. Stanley Riddell and his team used chimeric antigen receptors (CARs), technology that has previously been used within cancer research; however, their selective spin on the technology has yielded better results with fewer side effects.

Navigating Previous Concerns Involved with Immunotherapy

T cell therapy for cancer patients is not a new concept, but until recent technological advances it has not been overly successful. There are three main approaches to T cell therapy, including the modification of endogenous T cells receptors (TCR), introduction of new genetically modified TCR and the use of CAR T cells, which combine antibody-like recognition with T cell activating functions. Past clinical trials with all of these methods have provided proof of concept, yet they’ve only yielded short-term, mediocre results with a plethora of terrifying side effects, the most concerning being off-target reactivity and cytokine-release syndromes.1 As researchers move forward, the efficacy and side effects will remain a concern. Fortunately, technology has come a long way since this research began. Through the aid of advanced lab software scientists will be able to track and analyze data more easily, removing many of the bumps in the road on the way to clinical trial.

Researchers have identified that not all lymphocytes respond as desired in cancer. Although effector memory and effector T cells show promise in vitro, they are largely ineffective in vivo. Ideally, naive T cells would be used as they have the opportunity to become the cell that is most desirable, but upon the introduction of CARs they lose their naive quality. Researchers have observed that human stem cell-like memory T cells live longer within the body and retain their ability to differentiate, even in the presence of CARs.2 These more specialized cells are also advantageous as they can be used in far smaller quantities. It is important to acknowledge that these are injectable, living therapeutics. Although they not be inherently malicious, they can be opportunistic. Comprehensive lab software is indispensable in tracking the outcomes as this technology continues to move forward. Injectable therapy has the potential to reproduce uncontrollably upon entering the body, and if analysis is able to narrow the field of cells used by reducing dose or type, toxicity will be minimized and opportunities to proliferate will be reduced.

Better Selection Methods for T Cell Therapeutics

It’s becoming apparent that the best approach to minimizing many of the side effects associated with T cell therapy is to perform more stringent selection. In the past, researchers found a correlation between long-term survival and immunity of CD8+ T cells and their metabolic fitness. By using a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM), metabolically robust T cells can be selected based on their mitochondrial membrane potential.3 Scientists will be able to pare down the number of T cells that are required to be injected, by ensuring that those that are injected are viable over longer periods of time. With the aid of advanced lab software, analysis of these therapeutic solutions will be made easier, leading to ground-breaking medications. Metabolic potential selectivity brings researchers ever closer to a “live-in” long-term cancer drug—a therapeutic that could work to prevent relapse over the course of time. Additionally, this technology could be applied to human stem cell research for treatment in other illnesses along with their implications in cancer.

Dr. Riddell’s recent breakthrough was due to the acquisition of another company that produces reversible major histocompatibility complex (MHC) Streptamers. With the aid of innovative lab software, peptide antigen-presenting MHCs can be designed to select for antigen-specific T cells. The MHCs are joined together with a “Strep-tag,” which is composed of amino acid chains. The reversibility comes into play after selection, wherein scientists can wash the purified cells with a d-biotin solution to release the tag returning the T cells to their original state. By using this selection process on his team’s CAR therapeutics, a remission rate of more than 90% was observed in one of Riddell’s clinical trials. Although these results need to be approached with cautious optimism, this is a phenomenal proof of concept that is bound to lead to future clinical studies. Moving forward, the use of modern lab software will be important to the development of new tags, more selection methods and the analysis of the growth of current technologies.
BIOVIA Unified Lab Management provides a standardized approach for laboratory processes including management of procedures and resources. Additionally, it assists in the execution of lab workflows and tasks, which assists researchers in streamlining the optimization and development of biotherapeutic candidates. As research continues regarding immunotherapies, such as T cell therapies in cancer, effective lab software will prove to be indispensable, helping to save R&D dollars by cutting down time spent on analysis and prevent researchers from chasing poor leads. Current users are reporting a 35% reduction in analysis time and 25% improvement in productivity, accuracy and quality. Please contact us today to learn more about how BIOVIA software options can support the efforts of your lab.

  1.  “Genetically modified T cells in cancer therapy: opportunities and challenges,” 2015,
    http://dmm.biologists.org/content/8/4/337#sec-7
  2. “A human memory T cell subset with stem cell-like properties,” September 18, 2011, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192229/
  3. “Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy,” January 12, 2016, http://www.sciencedirect.com/science/article/pii/S1550413115005690