Cancer Vaccines: Bench to Bedside

Authors

  • Neha Tuli
  • Rachana Maniyar Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
  • Robert Bednarczyk Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
  • Ghada Ben Rahoma Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
  • Sarnath Singh Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
  • Jan Geliebter Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
  • Abraham Mittelman Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
  • Marc Wallack 1) Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA 2) Department of Surgery, Metropolitan Hospital Centre 1901 1st Avenue, New York, NY 10029, USA
  • Debabrata Banerjee Department of Pharmacology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
  • Raj K. Tiwari Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

DOI:

https://doi.org/10.13052/ijts2246-8765.2016.003

Keywords:

cancer vaccines, peptide epitopes, vaccinia virus – antigen retrieval

Abstract

The immune system has immense potential in cancer therapy as it is individualized, precision driven and robust, however, it is associated with challenges of its own that include immune evasion, development of tolerance and a sustained tumor rejection response. Recent FDA approval of several checkpoint inhibitors, anti-CTLA4, anti-PD-1, has re-invigorated cancer immunology by demonstrating that tolerance to cancer can be broken to induce a sustained immune response in patients. Active immunization with multivalent tumor associated antigens (TAA), however, is still a challenge. We have developed two specific distinct methods to generate multivalent antigens capable of tumor regression in prostate cancer and melanoma. In prostate cancer, we have generated specific multivalent peptide mimetics using phage display synthetic peptide libraries capable of metastatic tumor regression in an animal model. In melanoma, we have used a vaccinia virus based antigen retrieval technology to generate a multivalent antigenic vaccine. The antigenic repertoire is well defined. A protocol for the melanoma vaccine is FDA approved for clinical trials. We envision defining the humoral and cellular immune response to combine our active vaccine strategy with other treatment modalities including approved checkpoint inhibitors anti-CTLA4 and anti-PD-1. We believe our vaccine candidates are a new generation of immune-therapeutics that can prolong cancer free survival and prevent secondary recurrences. Our studies have challenged the existing paradigms to re-define cancer immunotherapy that bridges the gap between humoral and cellular immunity by combining active immune response with negative checkpoint inhibitors thus activating pre-existing dormant immune response.

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Author Biographies

Neha Tuli

N. Tuli is a Ph.D. candidate under the mentorship of Dr. Raj K. Tiwari at New York Medical College. Her curiosity in the medical sciences led her to enter medical school at Government Medical College (GMC, Surat, Gujarat, India) very early on in her career. After getting her M.B.B.S., Doctor of Medicine, in 2009, she practiced as a general physician and resident medical officer in private as well as government hospitals for 2 years. While working on a diphtheria project, her interest piqued towards the field of basic sciences and translational research. Subsequently, Dr. Tuli got her Master of Science in Pharmacology from New York Medical College in 2015. Her master research review was focused on metastatic castrate resistant prostate cancer. While pursuing her master’s, she worked as a research associate in cancer immunology with focus on thyroid cancer, melanoma and breast cancer. Currently, she is continuing her research aspirations as a Ph.D. candidate in Dr. Tiwari’s laboratory in Department of Microbiology and Immunology, New York Medical College. Her project focuses on thyroid tumor microenvironment – the mutual cooperation between inflammatory cells (including their secretome) and thyroid cancer epithelial cells to promote metastatic phenotype.

Rachana Maniyar, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

R. Maniyar is currently a graduate student in Dr. Tiwari’s laboratory at New York Medical College with a research focus in melanoma therapeutics. She completed her Bachelor’s degree from University of Mumbai, India in 2008 with a major in Life Sciences. Her interest in immunology propelled her to pursue her Master’s degree in Immunology from King’s College London, United Kingdom in 2009. Her master’s thesis focused on developing an antibody-antigen-adjuvant conjugate based dendritic cell vaccine for cancer immunotherapy. Following this, she worked in industry in India for five years in the field of regenerative medicine, focusing on product discovery and development in stem cells and growth factor concentrates. In an effort to further satiate her curiosity and desire to explore cancer immunotherapy, she entered the Ph.D. program in the Department of Microbiology and Immunology. Her current research focus centers on checkpoint inhibitors in melanoma therapy, their significance and possible ways to enhance their efficacies.

Robert Bednarczyk, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

R. Bednarczyk attended Loyola University Chicago as an undergraduate and earned a Bachelor of Science in Biology with Molecular Emphasis in 2009. Following his undergraduate studies, he volunteered at Advocate Christ Medical Center in Oak Lawn, Illinois from 2009–2010. Subsequently, he entered New York Medical College for graduate studies and earned a Master of Science in Microbiology and Immunology in 2012. His master’s thesis focused on Toxoplasma gondii, and its resistance to the innate immune response. To further pursue his research interests, he entered the Ph.D. program in the Department of Microbiology and Immunology program in the fall of 2012. His current research focuses on the importance of chronic inflammation as a major mediator of breast cancer development and progression. Specifically, focusing on the roles of pro-inflammatory tumor-associated macrophages (TAMs) including TAMs secretory factors – cytokines and exosomes, in breast cancer progression. During this time, he also worked as an adjunct instructor for Genetics Laboratory at Lander College for Men in the fall of 2015.

Ghada Ben Rahoma, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

G. Ben Rahoma graduated from the School of Medicine, Seventh of April University, Az-Zawiyah, Libya (August, 2006) with M.B.B.S, Doctor of Medicine. After graduation, she was employed as a general physician at Second of March Polyclinic, Az-Zawiyah, Libya (Oct, 2006–June, 2008). At the same time, she was working as a teaching assistant in the Department of Microbiology, School of Medicine, Seventh of April University, (2006–2008). Her passion for science coupled with hard work was awarded a Scholarship for Outstanding Teaching Assistant. In 2010, she started her Master’s program in the Department of Microbiology & Immunology, New York Medical College. Her master’s thesis involved development and application of a simple molecular rapid RT-PCR for detection and differentiation of Influenza A viruses. After finishing her master’s in May 2013, she was admitted to the Ph.D. program, Microbiology and Immunology Department, New York Medical College. Currently, she is working under the mentorship of Dr. Raj K. Tiwari, on using endothelial progenitor cell exosomes as a delivery platform for targeting tumor angiogenesis using antiestrogens.

Sarnath Singh, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

S. Singh earned his Ph.D. in Horiculture-Botany from the Banaras Hindu University in 1993 after finishing BSc (1985) and M.Sc (1988) from the same university. After completion of his doctorate, he started working as a junior research fellow in the Department of Botany, Banaras Hindu University. He quickly climbed the ladder to the position of Research Associate, having completed various projects sponsored by the Ministry of Environment and Forests as well as the Ministry of Coal, Govt. of India. Consequently, Dr. Singh bagged tenure position as a Senior Scientist and Head of the institution in Virendra Kumar Singh Krishi Vigyan Kendra, Unnao, Uttar Pradesh, India. For more than a decade, he worked as a material handler for 3M Canada Corporation in the healthcare division (2004–2016). Currently, he is a research associate coordinator at New York Medical College overlooking the clinical translational research projects.

Jan Geliebter, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

J. Geliebter is a professor in the Department of Microbiology and Immunology and Otolaryngology at New York Medical College. He received his undergraduate degree from Hebrew University of Jerusalem, Israel in Biology and his Doctorate from State University of New York Health Science Center at Brooklyn. His current research focus is papillary thyroid cancer, its molecular pathogenesis, and the effects of androgens on its progression and etiology. At New York Medical College Dr. Geliebter also holds the positions of Regional Vice President of the Executive Committee of Faculty Senate as well as the Course Director of the Medical Microbiology program. Loved by students and faculty alike, Dr. Geliebter has received numerous awards for this teaching and dedication as a mentor.

Abraham Mittelman, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

A. Mittelman is a practicing oncologist and an Associate Professor in the Department of Medicine, New York Medical College. He received his MD fromAutonomous University of Guadalajara in 1977. He completed his internship and residency from Downstate-Kings County Medical Center, Brooklyn, New York (1981). Subsequently he achieved fellowship in Oncology, rising to the ranks of Adjunct Attending in Development Chemotherapy, Memorial Sloan Kettering Cancer Center, New York, New York (1987). His research interest to treat cancers brought him to NewYork Medical College/Westchester County Medical Center, Valhalla, New York, quickly advancing from an assistant attending to an associate professor position. He is also cofounder and CEO of AV therapeutics whose mission is to bring significant immunobiologicals to the clinic.

Marc Wallack, 1) Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA 2) Department of Surgery, Metropolitan Hospital Centre 1901 1st Avenue, New York, NY 10029, USA

M. Wallack is the Chief of Surgery at Metropolitan Hospital, New York. He also holds the position of Vice-Chair of the Department of Surgery at New York Medical College. He received his MD from the University of Pittsburgh School of Medicine and completed his residency in general surgery from The University of Pennsylvania Health System. He has had an active practice for over 30 years. Dr. Wallack was instrumental in developing and clinically testing an FDA approved vaccinia virus based melanoma vaccine, and holds a patent for the same. His passion for research and improving patient health care is second to none.

Debabrata Banerjee, Department of Pharmacology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

D. Banerjee is an Associate Dean – Global Initiative, at Graduate School of Biomedical Sciences, Rutgers University. Professor Banerjee has contributed greatly towards studies in structural biology, stem cells, cancer and gene therapy with over a hundred scientific publications to his credit. He obtained Ph.D. in Biochemistry from Calcutta University. Subsequently, he completed his postdoctoral fellowship training in Biology from McGill University, Canada (1983–1987). He worked as a Senior Scientist for Research on Hematology and Blood Transfusion in Calcutta (1987–1989). He also held the position of Research Scientist, Molecular Pharmacology Laboratory at the Sloan-Kettering Institute of New York (1989–1992). His insightful vision and immense intellectual ability brought him to Rutgers University, New Jersey as an Associate Professor of Medicine and Pharmacology at Robert Wood Johnson Medical School. He is the author of five patents awarded for his ground breaking research.

Raj K. Tiwari, Departmentof Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA

R. K. Tiwari is a Professor of Microbiology and Immunology, and Professor of Otolaryngology at New York Medical College. He attained a Master of Science in Biochemistry (1979) and earned a Doctor of Philosophy in Biochemistry (1983) from Calcutta University, India. He held the position of an Assistant Attending Biochemist in the Sloan-Kettering Institute for Cancer Research (1989–1991) and consequently was appointed as anAssistant Professor of Biochemistry in Department of Surgery at Cornell University Medical College, New York (1991–1996). Dr. Tiwari has mentored numerous undergraduate and graduate (M.S. and Ph.D.) students. He has been a Graduate Program Director for the Department of Microbiology and Immunology for over 15 years, always looking out for the students’ best interest and providing them with the opportunity to acquire analytical skills for a career in academia, industry or translational research. Dr. Tiwari is a leader in cancer prevention and control with over 25 years of experience in cancer biology. His current research focuses on understanding the role of inflammation in breast and thyroid cancer specifically mitigated by infiltrating macrophages, as well as checkpoint inhibitors in melanoma therapy. In addition, Dr. Raj K. Tiwari is currently the Chief Scientific Officer of AV Therapeutics (2013–present) and is inventor of several patents involving Capridine and Cancer Vaccine.

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Published

2016-04-25

How to Cite

Tuli, N., Maniyar, R., Bednarczyk, R., Rahoma, G. B., Singh, S., Geliebter, J., Mittelman, A., Wallack, M., Banerjee, D., & Tiwari, R. K. (2016). Cancer Vaccines: Bench to Bedside. International Journal of Translational Science, 2016, 33–60. https://doi.org/10.13052/ijts2246-8765.2016.003

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Volume 2016

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Articles