Advaxis, Inc. ADXS,
a biotechnology company developing cancer immunotherapies, announced the
publication of preclinical research with its lead candidate, ADXS-HPV for the
treatment of HPV-associated cancers in the journal, Cancer Immunology
Research. In this publication, researchers at the National Cancer Institute
(NCI) reported on the biologic mechanisms behind the unique ability of
ADXS-HPV to decrease the immunosuppressive activity of Tregs in the tumor
microenvironment that result in increased anti-tumor activity. This research
demonstrates the critical role of the tLLO peptide fusion and the strong
adjuvant effect of tLLO as contributing to the increase in activated T-cells
and the relative decrease in the number of Tregs in tumors, thereby increasing
anti-tumor activity.
The research was conducted by Dr. Zhisong Chen, Dr. Samir Khleif and their
research team at the Vaccine Branch, center for Cancer Research, NCI, NIH. The
research was supported by the Intramural Research Program of the Center for
Cancer Research, NCI, NIH and funded in part by Advaxis through a
collaborative research and development agreement. The publication, entitled,
"Episomal expression of a truncated listeriolysin O (LLO) in LmddA-LLO-E7
vaccine enhances anti-tumor efficacy by preferentially inducing CD4+FoxP3- T
cell and CD8+ T cell expansion," by Drs. Chen, Ozbun, Chong, Wallecha,
Berzofsky, and Khleif, reported the complete regression of tumors in about 40%
of mice after two vaccinations with ADXS-HPV. Furthermore, with the exception
of one, these mice survived at least six months without relapse.
"This preclinical study conducted by researchers at the NCI further
demonstrates how our proprietary Listeria-based cancer immunotherapy platform
works, altering the microenvironment within the tumor to shrink, and in some
cases, completely eliminating the tumor," said Daniel J. O'Connor, Advaxis
Chief Executive Officer. "Advaxis's proprietary fusion with tLLO and the
adjuvant effect of LLO in ADXS-HPV induced the strongest tumor regression."
In this preclinical study, Advaxis's Lm-based immunotherapies decreased the
proportion of Tregs cells in tumors by causing preferential expansion of
CD4+FoxP3- (activated) T cells and CD8+ Foxp3- (activated) T cells first in
the blood and lymphoid tissue of the mice, and subsequently infiltrating the
tumors and improving the ratio of activated T cells to Tregs inside the tumor
microenvironment hereby enabling HPV targeted killer Tcells to eliminate the
tumor. This activity was reported to be due to a mechanism dependent on and
directly mediated by LLO, which was confirmed using a recombinant Lm where LLO
was replaced with cytolysin Perfringolysin O (PFO) allowing exit of this
strain from the phagolysosome.
"These results mark progress in our understanding of the potential mechanism
behind the unique clinical activity of ADXS-HPV that has been associated with
CRs, PRs and apparent prolonged survival as a single agent in recurrent
cervical cancer in clinical trials," commented Dr. Robert Petit, Chief
Scientific Officer of Advaxis. "The results are better than those achieved in
earlier studies with different (non-Advaxis) Lm-based immunotherapies. They
suggest that tLLO serves as a promising adjuvant and that its incorporation
into ADXS-HPV is a critical contributor to the changes in the tumor
microenvironment that favor immune killing of the tumor cells."
ADXS-HPV is in clinical trials for three HPV-associated cancers: cervical
cancer, head and neck cancer and anal cancer. Advaxis reported final Phase 2
data in recurrent cervical cancer at the 2014 American Society of Clinical
Oncology (ASCO) Annual Meeting and plans to move forward with a registration
program in recurrent cervical cancer.
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