Advertisement

 

 

Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.
Author Information (click to view)

Shrimali R, Ahmad S, Berrong Z, Okoev G, Matevosyan A, Razavi GSE, Petit R, Gupta S, Mkrtichyan M, Khleif SN,


Shrimali R, Ahmad S, Berrong Z, Okoev G, Matevosyan A, Razavi GSE, Petit R, Gupta S, Mkrtichyan M, Khleif SN, (click to view)

Shrimali R, Ahmad S, Berrong Z, Okoev G, Matevosyan A, Razavi GSE, Petit R, Gupta S, Mkrtichyan M, Khleif SN,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Journal for immunotherapy of cancer 2017 08 155(1) 64 doi 10.1186/s40425-017-0266-x

Abstract
BACKGROUND
We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment.

METHODS
Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations.

RESULTS
We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4(+) and CD8(+) T cells along with a decrease of inhibitory cells.

CONCLUSION
To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall efficacy of cancer immunotherapy.

Submit a Comment

Your email address will not be published. Required fields are marked *

18 − 11 =

[ HIDE/SHOW ]