M.Sc Biochemistry, University of Madras
Ph.D., in Biochemistry-Molecular Oncology, University of Madras
> Dendritic cell-based immunotherapy
> Tumor infiltrating cell-based immunotherapy
> CAR-T cell therapy
> Tumor microenvironment
Core area of Research – Cancer Immunotherapy
Cancer immunotherapy was voted as the “breakthrough of the year” by the journal Science, in 2013 and has revolutionized the field of oncology. Our stint with Immunotherapy began in the year 2003 with a DBT funded project on dendritic cell vaccines for HPV positive cervical cancer, which led to a Phase I trial. This was the first immune cell based clinical trial in the country. Following this, Phase II trials in cervical and ovarian cancer were initiated. Our current interest is on developing point of care cell therapies indigenously, backed by cutting edge research and state of art molecular tools.
A GMP compliant, large scale generation protocol is essential for ensuring the success of cell based immunotherapy. Our objective was to establish a common, scaled-up protocol to generate clinical grade DCs using two different antigenic sources- either autologous tumor lysates (TL) or recombinant human SPAG9 (rhSPAG9) protein. We also developed a harmonized quality control (QC) criteria based on the attributes that reflect their functional and phenotypic efficacy. For the Phase II clinical trial, after obtaining an Institutional Ethics committee-approved informed consent, eighteen patients
were randomized to receive, along with concurrent chemo-radiotherapy, either placebo, TL or rhSPAG9 primed DC. Our results showed that scaling up DC cultures from plates to surface coated culture bags increased mature DC yields consistently without compromising their phenotypic or functional efficacy. Our QC criteria which included the evaluation of several key attributes, confirmed that irrespective of antigenic source used for priming, mature DCs expressed six-fold higher levels of CD83, compared to immature DCs and were functionally efficient in inducing proliferation and IFNꝩ synthesis in allogenic responders. Tracking the viability and phenotype of cryopreserved DCs showed that MDCs had >90% viability for up to three years while a mature DC phenotype was retained for up to one year, using our common harmonized protocol. Our large-scale, clinical grade DC generation method for cellular immunotherapy, showed that two markedly different antigenic sources could be used effectively for maturation of DCs in culture bags using a common protocol without compromising on phenotypic and functional capacity of the resulting mature DC.
TNBC represents approximately 10–15% of all breast cancers and patients with TNBC have a poor outcome compared to the other subtypes of breast cancer. TNBC is considered to be immunologically cold as the expression of Immune checkpoint inhibitors like PD-1, PDL1 and Indoleamine 2,3, dioxygenase may cause death or suppression of infiltrating immune cells. Indoleamine 2, 3 dioxygenases (IDO1and 2), are found to be increased within dendritic cells, triple negative breast cancer cells as well as other cells in the tumor microenvironment. They belong to the family of enzymes that catabolize the first and rate limiting step of tryptophan metabolism along the L-kynurenine pathway. IDO1 expression is associated with the death of lymphocyte and NK cell populations, facilitating the infiltration of regulatory T cells as well myeloid derived suppressors. The current study focusses on improving the efficacy of the Dendritic cell vaccines by targeting IDO activity during maturation, that may enhance the functional efficacy of the DCs which may otherwise suppress responses and improve outcomes in patients who receive dendritic cell vaccine therapy.
In cancer, circulating immune complexes (CICs) are formed by the binding of tumor-associated antigens (TAAs) with their corresponding autoantibodies. These complexes can modulate immune responses through interactions with Fc receptors on immune cells, and their immunological impact is influenced by the nature of the associated antigens. This study aimed to standardize the isolation of CICs from serum and plasma samples of cervical cancer patients, validate the presence of immunoglobulins, and characterize the antigenic composition using mass spectrometry-based proteomics.
Funding agency: DST–SERB Role: PI
Status: Completed – July 2025
Funding agency: DST Role: Co-PI
Status: Completed
Funding agency: ICMR Role: Co-PI
Status: Ongoing
Other Publications
M.Tech Biotechnology
Research ScholarVaishnave joined as a Junior Research fellow under an ICMR-CAR grant and is currently in the final year of PhD in Molecular oncologyM.Sc Medical Biochemistry
Research ScholarAnusha began her PhD, working as a Junior Research Fellow under a DST-SERB funded grant and is currently working in the third year of PhD.B. Tech Genetic Engineering and M.Sc in Cancer Cell biology (Sussex University-UK).
InternAnish is currently an intern in the department gaining experience as well as contributing towards immune cell culture and assay development.Open Positions: NOT OPEN CURRENTLY
Lab Culture: The immunotherapy unit functioning within the Dept of Molecular Oncology nurtures an environment of independent thinking and growth, fostered by a strong understanding of the basics and a love for immunology. We have hosted biochemists, biotechnologists, genetic engineers and cancer biologists who had an innate curiosity to solve the riddles of cancer through the immune system. We also harbour an environment where students are encouraged to explore new technologies, platforms and techniques independently, gaining confidence and expertise in the process.
To apply visit https://cancerinstitutewia.in/career/