Profile:
Tania Jain, MBBS
Johns Hopkins School of Medicine, Baltimore, MD, USA
Introducing Dr. Tania Jain
Dr. Tania Jain’s fascination with science began in her childhood as a way to explain the world around her. However, as she delved deeper into medicine, she gravitated towards a specialty filled with unanswered questions.
“What drew me to oncology was the limited availability of treatments and the limited access to treatment,” explains Jain. Inadequate treatment options, coupled with the physical, emotional and financial challenges, create a heavy burden for patients.
Now a physician-scientist at Johns Hopkins, Jain is the director of the adult CAR T program (chimeric antigen receptors) for hematological malignancies. In this role she has the chance to explore novel hypotheses born at the bedside.
Jain goes beyond routine medical practices. Whenever possible and with permission, she collects an extra tube of aspirate during bone marrow biopsies on her patients. It’s a win-win. Patients can contribute to research efforts, and the samples are invaluable to helping her survey the frontiers of rare blood cancers like myeloproliferative neoplasms (MPNs).
Innovating Clinical Tools: Jain’s MPN Challenge™ award
Dr. Jain’s career as a physician-scientist seamlessly integrates clinical practice with innovative research. She emphasizes the influence of her clinical work on her scientific studies: “It continues to remind you that whatever you develop, whatever you learn about, whatever you scientifically investigate, has to have that impact in the real world where it matters.” Her dual role empowers her to develop the very therapies she hopes to see implemented in her clinic.
Funded by an MPN Research Foundation’s (MPNRF) 2024 MPN Challenge™ award, Jain’s latest project exemplifies this integration. Titled Immunotherapeutic targeting of signaling lymphocytic activation molecule family 7 (SLAMF7) in myeloproliferative neoplasms (MPNs), the project capitalizes on her expertise in CAR T-cell therapy and the latest MPN research findings. “MPN and cellular therapy… they live in two parallel universes right now,” she explains. “Myelofibrosis (MF) certainly takes a back seat in terms of priority within the scope of hematological malignancies, which is why foundations like MPNRF are critical to the progress of MPNs.”
MPN Challenge puts MPNs in the spotlight, giving them center stage during treatment development. This funding allows Jain to merge the parallel universes of cutting-edge cellular therapy and the unique challenges of MPNs, potentially improving long-term outcomes for these patients.
Understanding Fibrocytes: Key players in myelofibrosis
One of Dr. Jain’s key research interests is myelofibrosis (MF), a rare and often debilitating chronic blood cancer. MF features a significant structural change in the environment of bone marrow, the site of blood cell production known as hematopoiesis.
Fibrocytes are a type of cell that constitute less than 1% of the bone marrow, and, according to new research, they appear to significantly impact the severity and progression of MF. “The fibrocytes create a mesh of fibers in the bone marrow or inside the bones…which makes the bone marrow less soft or less juicy, which is how a healthy bone marrow would look and what is needed for normal hematopoiesis,” Jain explains. Despite their crucial role, many aspects of these cancerous fibrocytes remain a mystery, including their origins and specific characteristics.
Discovering SLAMF7: A potential game-changer in myelofibrosis treatment
In 2019, Dr. Jain came across an exciting discovery featured in a scientific review paper aptly titled SLAM Dunk in Myelofibrosis. Recent research identified signaling lymphocyte activation molecular F7 (SLAMF7), a molecule located specifically on the surface of cancer-associated cells in MF patients.
Through discussions with colleagues, Jain realized SLAMF7’s potential to enhance her CAR T-cell therapy research. “The fact that SLAMF7 is expressed on fibrocytes and the clonal monocytes in myelofibrosis is not just a matter of chance and is something that can actually be exploited in a therapeutic manner,” Jain notes with excitement.
CAR T-cell therapy is highly effective at training the immune system to identify cancer cells. The challenge lies in identifying the right molecule to target. With the crosshatches of CAR T-cells focused on a rare molecule only expressed on cancer cells, there’s minimal risk that immune cells will mistakenly attack healthy cells. Importantly, this lowers the treatment’s toxicity for patients.
Targeting SLAMF7 could be a game-changer in MF diagnosis, prognosis, or potentially serving as a target for drug development.
Collaboration and Innovation: Jain’s team approach to medical research
Dr. Jain prides herself on her ability to unite experts from diverse fields to collaboratively address complex questions in medical research. For her current project, she assembled a team that includes Dr. Linda Resar, an expert with extensive experience developing mice with MF-like symptoms for study, and Dr. Saad Kenderian, a pioneer in CAR T-cell therapy.
Their hypothesis is bold yet promising: targeting SLAMF7 with CAR T-cells could restore marrow function by reducing fibrosis, thereby improving patient outcomes.
SLAMF7 research is still in its infancy but recent research points towards SLAMF7 as a potential measure of MF severity. The bone marrow samples collected by Dr. Jain will be meticulously processed and analyzed. She and her collaborators are currently determining the most effective method for detecting the unique molecule. Proper detection is the first step towards using SLAMF7 as a biomarker or therapeutic target.
Conclusion: Dr. Jain’s vision for the future of MPN treatment
Dr. Jain exemplifies the duality of a physician-scientist: driven to help patients while maintaining a realistic perspective on the challenges ahead. With a balanced outlook, Jain readily shares the hope that her efforts would benefit “a meaningful percentage” of her patients, but also pragmatically adds “though I know it’s not 100%.”
Jain’s 2024 MPN Challenge™ project has the potential to provide MF patients with a promising new treatment. With new discoveries in CAR T-cells emerging every day, researchers and clinicians at the frontiers of oncology, like Jain, are expanding the life-saving options available to their patients.
Jain displays dedication, innovation, and an unwavering commitment to improving the lives of those affected by rare blood cancers. “It will be an uphill task to get to the point where we can apply cellular therapy in the context of myelofibrosis or malignant neoplasms.” Yet, her optimism shines through when discussing her patients. “Introducing an intervention that helps mitigate that constellation of suffering, so to speak, it’s certainly beautiful to watch.” This hope, coupled with her scientific rigor, drives her forward.
Sources:
Jain, T., Olson, T. S., & Locke, F. L. (2023). How I treat cytopenias after CAR T-cell therapy. In Blood (Vol. 141, Issue 20). https://doi.org/10.1182/blood.2022017415
Sakemura, R., Hefazi, M., Siegler, E. L., Cox, M. J., Larson, D. P., Hansen, M. J., Manriquez Roman, C., Schick, K. J., Can, I., Tapper, E. E., Horvei, P., Adada, M. M., Bezerra, E. D., Kankeu Fonkoua, L. A., Ruff, M. W., Nevala, W. K., Walters, D. K., Parikh, S. A., Lin, Y., … Kenderian, S. S. (2022). Targeting cancer-associated fibroblasts in the bone marrow prevents resistance to CART-cell therapy in multiple myeloma. Blood, 139(26). https://doi.org/10.1182/blood.2021012811
Maekawa, T., Kato, S., Kawamura, T., Takada, K., Sone, T., Ogata, H., Saito, K., Izumi, T., Nagao, S., Takano, K., Okada, Y., Tachi, N., Teramoto, M., Horiuchi, T., Hikota-Saga, R., Endo-Umeda, K., Uno, S., Osawa, Y., Kobayashi, A., … Kimura, F. (2019). Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab. Blood, 134(10). https://doi.org/10.1182/blood.2019000051
Marcellino, B. K., & Mascarenhas, J. (2019). SLAM dunk for myelofibrosis? In Blood (Vol. 134, Issue 10). https://doi.org/10.1182/blood.2019002119
Verstovsek, S., Manshouri, T., Pilling, D., Bueso-Ramos, C. E., Newberry, K. J., Prijic, S., Knez, L., Bozinovic, K., Harris, D. M., Spaeth, E. L., Post, S. M., Multani, A. S., Rampal, R. K., Ahn, J., Levine, R. L., Creighton, C. J., Kantarjian, H. M., & Estrov, Z. (2016). Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis. Journal of Experimental Medicine, 213(9), 1723–1740. https://doi.org/10.1084/jem.20160283