UCLA researchers in the department of microbiology, immunology and molecular genetics have discovered the immune boosting benefits of creatine in disease models.
BACKGROUND:
T-cells are centrally important in mediating immune response against cancer, and have as no surprise become attractive therapeutic targets to treat cancer. T-cell responses require great amounts of ATP which are produced through distinct metabolic programs. However, in the tumor microenvironment there exists fierce competition for nutrients against fast growing tumor cells. This requires T-cells to utilize efficient and economical bioenergy metabolism to mount an effective anti-cancer response. Currently, there are many efforts to determine an effective small molecule treatment to allow T-cells to mount more effective anti-cancer responses by increasing the amount of available nutrients for ATP synthesis.
However, current small molecules have focused on cancer metabolism have faced many criticisms about self-selecting for immune cancer cells. Other efforts for development of small molecules for rewiring T-cell metabolism have been shown to have unwanted off-target effects. Recent interest has been generated in the development of treatments that utilize naturally occurrent biomolecules. These treatments can be given to patients without much worry to off-target effects and given conveniently in the form of oral tablets. The other major benefit of naturally occurring biomolecules is the non-ability for cancer cells to develop an immunity to their use. Therefore, it is of interest to determine a course of cancer therapy that utilizes natural biomolecules that will allow T-cells to produce more ATP for increased metabolic activity.
INNOVATION:
Dr. Yang at UCLA has discovered that creatine is a critical molecule buffering ATP levels in cancer targeting CD-8+ T-cells through maintaining a readily available high energy phosphate reservoir. The use of creatine as a dietary substance was even shown to suppress tumor growth in multiple mouse tumor models. Beyond this initial observation, creatine supplementation as part of a combination cancer immunotherapy (e.g. combining with PD-1/PD-L1 immune checkpoint inhibitor blocade therapy) showed even greater tumor suppression efficacy. This discovery highlights a powerful use of a common health supplement as a “molecular battery” that conserves bioenergy to power antitumor T-cell immunity, underscoring its potential of supplementation to improve T-cell based cancer immunotherapies.
POTENTIAL APPLICATIONS:
• Anti-tumor treatment (either as a single agent or combinatorial approach)Use of creatine as an immune boosting health supplement (tested claim)
• Use of creatine to boost T-cell activity after allogenic stem cell transplantation
• Use of creatine to boost CAR-T cell activity (CD-8+) after transplantation
ADVANTAGES:
• Natural biomolecule that allows for: easy introduction (oral delivery and convenience of large amounts of pre-existing products), and less worries of acquired immunity.
• Use of pre-existing product that can be marketed easily
• Wide range of application for disease models or as a general health supplement
DEVELOPMENT-TO-DATE:
The finding has been shown in pre-clinical cancer models to work in the specified manner but has not yet been published.