Lab In The News
Innovative Synthetic DNA-based Cancer Immunotherapy Approach Shows Tumor-clearing Ability in Preclinical Models
PHILADELPHIA — (April 18, 2019) — Wistar scientists have developed a novel synthetic DNA approach for patient-specific production of cancer-targeting molecules called bispecific T cell engagers.
The Muthumani Laboratory
There are still many deadly diseases without approved vaccines. Over the past 25 years, multiple platforms have been developed in attempts to create vaccines that can effectively induce protective immunity to these pathogens. One promising platform is DNA vaccination, the safety of which has been well documented in numerous clinical settings. The simplicity of DNA plasmid engineering and production as compared to that of live attenuated and killed viral vaccines makes DNA vaccines an attractive technology. Unlike traditional vaccines, DNA vaccines are very stable at ambient temperatures and therefore are ideal candidates for distribution in resource-poor communities where serious infectious pathogens remain endemic and traditional vaccines would require a cold-chain for transportation and storage. The research of the Muthumani laboratory is expected to yield synthetic DNA constructs that can be administered alone or in combination with biological monoclonal antibodies (mAbs) to offer broad, rapid, and sustained protection against pathogen and cancer targets.
Peng Xiao, Ph.D.
Directing immune responses against emerging infectious diseases
The lab specializes in the development of novel DNA vaccines and therapeutics that target emerging infectious diseases. Using enhanced DNA technology, the lab has designed DNA vaccines that drive immune responses in prophylactic or therapeutic settings against Human Immunodeficiency Virus (HIV), Dengue (DV), Chikungunya virus (CHIKV), Middle Eastern Respiratory Syndrome (MERS) virus, and Zika Virus (ZV). The lab is characterizing the quantity and quality (i.e. B and T cell) of the immune responses induced or generated by these DNA plasmids in order to improve their ability to mediate virus neutralization and clearance.
Development of a novel plasmid-encoded IgG immunotherapeutic platform as a new tool for cancer treatment
The lab is developing a novel gene delivery system to produce anti-tumor and immunomodulatory antibodies in vivo for cancer treatment. This approach may be less expensive than existing anti-tumor monoclonal antibody delivery methods. Additionally, delivering these antibodies with DNA plasmid technology may increase duration of antibody expression in vivo and allowing for simple combination formulations in the absence of a host anti-vector immune response. Some targets of interest include the tumor antigens HER2 and PSMA, as well as the immune checkpoint proteins PD-1 and Lag3.
Tebas, P., Roberts, C.C., Muthumani, K., Reuschel, E.L., Kudchodkar, S.B., Zaidi, F.I., White, S., Khan, A.S., Racine, T., Choi, H., Boyer, J., Park, Y.K., Trottier, S., Remigio, C., Krieger, D., Spruill, S.E., Bagarazzi, M., Kobinger, G.P., Weiner, D.B., Maslow, J.N."Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report." N Engl J Med. 2017 Oct 4. doi: 10.1056/NEJMoa1708120. [Epub ahead of print]
Griffin, B.D., Muthumani, K., Kobinger, G.P., et al. "DNA vaccination protects mice against Zika virus-induced damage to the testes." Nat Commun. 2017 Jun 7;8:15743. doi: 10.1038/ncomms15743.
Muthumani, K., Griffin, B.D., Weiner, D.B., et al. "In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine." NPJ Vaccines. 2016 Nov 10;1:16021. doi: 10.1038/npjvaccines.2016.21. eCollection 2016.
Muthumani, K., Block, P., Weiner, D.B., et al. "Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus." J Infect Dis. 2016 Aug 1;214(3):369-78. doi: 10.1093/infdis/jiw111. Epub 2016 Mar 21.
Muthumani, K., Falzarano, D., Weiner, D.B., et al. "A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates." Sci Transl Med. 2015 Aug 19;7(301):301ra132. doi: 10.1126/scitranslmed.aac7462.