Priya Ramanathan

Academics & Training

M.Sc Biochemistry, University of Madras Ph.D., in Biochemistry-Molecular Oncology, University of Madras

Research Interest

> Dendritic cell-based immunotherapy > Tumor infiltrating cell-based immunotherapy > CAR-T cell therapy > Tumor microenvironment

Overview

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.

• Dendritic cell based immunotherapy

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.

• Studies on improving the efficacy of dendritic cell vaccines by targeting Indoleamine 2, 3, dioxygenase in triple negative breast cancers

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.

• Role of autoantibodies and circulating immune complexes in cervical and ovarian cancer

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.

Ongoing Projects

Studies on improving the efficacy of dendritic cell vaccines by targeting indoleamine 2,3-dioxygenase 1 and 2

Funding agency: DST–SERB Role: PI

Status: Completed – July 2025

ID-PPP-OTN: Infrastructure and development of technologies for pre-clinical evaluation, product establishment and platform integration for onco-theranostic applications

Funding agency: DST Role: Co-PI

Status: Completed

Screening and identification of hormone receptor-bound tissue-specific co-regulator complex proteins as novel therapeutic targets and subsequent drug repurposing in cervical cancer

Funding agency: ICMR Role: Co-PI

Status: Ongoing

• Hascitha, J., Priya, R., Jayavelu, S., Dhandapani, H., Selvaluxmy, G., Sunder Singh, S., & Rajkumar, T. (2016). Analysis of Kynurenine/Tryptophan ratio and expression of IDO1 and 2 mRNA in tumour tissue of cervical cancer patients. Clinical Biochemistry, 49(12), 919–924. https://doi.org/10.1016/j.clinbiochem.2016.04.008

• Ramanathan, P., Ganeshrajah, S., Raghanvan, R. K., Singh, S. S., & Thangarajan, R. (2014). Development and Clinical Evaluation of Dendritic Cell Vaccines for HPV Related Cervical Cancer – a Feasibility Study. Asian Pacific Journal of Cancer Prevention, 15(14), 5909–5916. https://doi.org/10.7314/apjcp.2014.15.14.5909

• Ramanathan, P., Dhandapani, H., Jayakumar, H., Seetharaman, A., & Thangarajan, R. (2018). Immunotherapy for cervical cancer: Can it do another lung cancer? Current Problems in Cancer, 42(2), 148–160. https://doi.org/10.1016/j.currproblcancer.2017.12.004

• Dhandapani, H., Jayakumar, H., Seetharaman, A., Singh, S. S., Ganeshrajah, S., Jagadish, N., Suri, A., Thangarajan, R., & Ramanathan, P. (2021). Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4+, CD8+ T cells and activate NK cells: a potential candidate molecule for immunotherapy in cervical cancer. Cancer Cell International, 21(1). https://doi.org/10.1186/s12935-021-01951-7

• Dhandapani, H., Seetharaman, A., Jayakumar, H., Ganeshrajah, S., Singh, S. S., Thangarajan, R., & Ramanathan, P. (2021). Autologous cervical tumor lysate pulsed dendritic cell stimulation followed by cisplatin treatment abrogates FOXP3+ cells in vitro. Journal of Gynecologic Oncology, 32(4). https://doi.org/10.3802/jgo.2021.32.e59

• Ramanathan, P., Dhandapani, H., Jayakumar, H., Ganeshrajah, S., & Thangarajan, R. (2014). Dendritic cells primed with HPV positive cervical tumor lysate are superior to unprimed DCs in migratory capacity and induce a potent Th1 response. Human Immunology, 75(12), 1216–1224. https://doi.org/10.1016/j.humimm.2014.09.020

Other Publications

• Rao, A. K. D. M., Arvinden, V. R., Ramasamy, D., Patel, K., Meenakumari, B., Ramanathan, P., Sundersingh, S., Sridevi, V., Rajkumar, T., Herceg, Z., Gowda, H., & Mani, S. (2021). Identification of novel dysregulated circular RNAs in early‐stage breast cancer. Journal of Cellular and Molecular Medicine, 25(8), 3912–3921. https://doi.org/10.1111/jcmm.16324

• Kodous, A. S., Balaiah, M., & Ramanathan, P. (2023). Single cell RNA sequencing – a valuable tool for cancer immunotherapy: a mini review. Oncologie, 25(6), 635–639. https://doi.org/10.1515/oncologie-2023-0244

• Oviya, R. P., Thangaretnam, K. P., Ramachandran, B., Ramanathan, P., Jayavelu, S., Gopal, G., & Rajkumar, T. (2022). Mitochondrial ribosomal small subunit (MRPS) MRPS23 protein–protein interaction reveals phosphorylation by CDK11-p58 affecting cell proliferation and knockdown of MRPS23 sensitizes breast cancer cells to CDK1 inhibitors. Molecular Biology Reports, 49(10), 9521–9534. https://doi.org/10.1007/s11033-022-07842-y

• Natarajan, V., Ramanathan, P., Gopisetty, G., Ramachandran, B., Thangarajan, R., & Kesavan, S. (2018). In silico and in vitro screening of small molecule Inhibitors against SYT-SSX1 fusion protein in synovial sarcoma. Computational Biology and Chemistry, 77, 36–43. https://doi.org/10.1016/j.compbiolchem.2018.09.006

• Thangaretnam, K. P., Paramasivam, O. R., Ramanathan, P., Gopisetty, G., & Rajkumar, T. (2018). Production and characterization of monoclonal antibodies against recombinant extracellular domain of CD99. Human Antibodies, 27(1), 69–83. https://doi.org/10.3233/hab-180350

• Arvinden, V. R., Magendhra Rao, A. K. D., Meenakumari, B., Ramanathan, P., Sundersingh, S., Sridevi, V., Rajkumar, T., Herceg, Z., & Mani, S. (2018). RNA sequencing identifies dysregulated circular RNAs in early-stage breast cancer. Cold Spring Harbor Laboratory. https://doi.org/10.1101/506246

• Thangaretnam, K. P., Gopisetty, G., Ramanathan, P., & Rajkumar, T. (2017). A polypeptide from the junction region sequence of EWS-FLI1 inhibits Ewing’s sarcoma cells, interacts with the EWS-FLI1 and partner proteins. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-07482-4

• Gopisetty, G., Rangarajan, A., Natarajan, T., Lakshminarayanan, S., Singh, S. S., Subramani, J., Ramanathan, P., & Seshadri, R. A. (2025). HIPK2 exhibits context dependent dualistic effects and combinational inhibition of HIPK2-NLK-MAPK11 axis manifests synergism against gastric cancer. Springer Science and Business Media LLC. https://doi.org/10.21203/rs.3.rs-7795753/v1

• 9. Seetharaman, A., Duraisamy, P., Ariraman, S., Ramanathan, P., & Sudhakar, S. (2025). Nanoarchaeosomes loaded with tumor antigens elicit antigen-presenting cell activation and T cell response for cervical cancer immunotherapy. Materials Advances. https://doi.org/10.1039/d5ma01014d

Ms. Vaishnave Sakthi Prasad

M.Tech Biotechnology

Ms. Anusha Jayachandar

M.Sc Medical Biochemistry

Mr. Anish Kumaran

B. Tech Genetic Engineering and M.Sc in Cancer Cell biology (Sussex University-UK).

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 /career

Contact: PI/Lab email

r.priya@cancerinstitutewia.org