T cell-mediated immune responses are central to effective anti-tumor immunotherapy. T cell receptors (TCRs) recognize tumor-derived peptides presented by human leukocyte antigens (HLA), thereby triggering T cell activation and subsequent lysis of malignant cells. TCR-based adoptive therapies are increasingly entering clinical practice. However, limitations such as insufficient T cell persistence, antigen loss, and further immune escape mechanisms continue to hamper durable therapeutic responses.
Distinct TCRs can mediate markedly different qualities of tumor control, depending on their intrinsic binding properties. Our research group focuses on optimizing target antigen selection, TCR validation, and the enhancement of effector cell resilience. Cancer-related peptides identified through mass spectrometry-based immunopeptidomics or in silico binding predictions are leveraged to isolate TCRs with high potential for clinical translation.
To elucidate key determinants of effective T cell responses, we employ single-cell RNA and TCR sequencing, flow cytometry, and functional cell-based assays. In parallel, we investigate novel delivery strategies, including in vivo T cell engineering using lipid nanoparticles (LNPs). TCR-engineered T cells are further optimized through combinatorial approaches integrating pharmacological modulation. Overall, our research aims to accelerate the translation of TCR-based therapies into clinical applications for both solid and hematologic malignancies.
- Fuchsl, F.*, Untch, J.*, Kavaka, V., Zuleger, G., Braun, S., Schwanzer, A., Jarosch, S., Vogelsang, C., de Andrade Kratzig, N., Gosmann, D., Ollinger, R., Giansanti, P., Hiltensperger, M., Rad, R., Busch, D. H., Beltran, E., Braunlein, E.‡, & Krackhardt, A. M.‡ (2024). High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells. Nat Commun, 15(1), 10520. *Equal contribution; ‡Joint supervision. [open access]. https://doi.org/10.1038/s41467-024-53911-0.
- Tretter, C.*, de Andrade Kratzig, N.*, Pecoraro, M., Lange, S., Seifert, P., von Frankenberg, C., Untch, J., Zuleger, G., Wilhelm, M., Zolg, D. P., Dreyer, F. S., Braunlein, E., Engleitner, T., Uhrig, S., Boxberg, M., Steiger, K., Slotta-Huspenina, J., Ochsenreither, S., von Bubnoff, N., Bauer, S., Boerries, M., Jost, P. J., Schenck, K., Dresing, I., Bassermann, F., Friess, H., Reim, D., Grutzmann, K., Pfutze, K., Klink, B., Schrock, E., Haller, B., Kuster, B., Mann, M., Weichert, W., Frohling, S., Rad, R., Hiltensperger, M. ‡, Krackhardt, A. M. ‡ (2023). Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification. Nat Commun, 14(1), 4632. *Equal contribution; ‡Joint supervision [open access]. https://doi.org/10.1038/s41467-023-39570-7.
- Rejeski, K., Hansen, D. K., Bansal, R., Sesques, P., Ailawadhi, S., Logue, J. M., Braunlein, E., Cordas Dos Santos, D. M., Freeman, C. L., Alsina, M., Theurich, S., Wang, Y., Krackhardt, A. M., Locke, F. L., Bachy, E., Jain, M. D., Lin, Y., & Subklewe, M. (2023). The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma. J Hematol Oncol, 16(1), 88. [open access]. https://doi.org/10.1186/s13045-023-01465-x
- Braunlein, E.*, Lupoli, G.*, Fuchsl, F., Abualrous, E. T., de Andrade Kratzig, N., Gosmann, D., Wietbrock, L., Lange, S., Engleitner, T., Lan, H., Audehm, S., Effenberger, M., Boxberg, M., Steiger, K., Chang, Y., Yu, K., Atay, C., Bassermann, F., Weichert, W., Busch, D. H., Rad, R., Freund, C., Antes, I., Krackhardt, A. M. (2021). Functional analysis of peripheral and intratumoral neoantigen-specific TCRs identified in a patient with melanoma. J Immunother Cancer, 9(9). *Equal contribution [open access]. https://doi.org/10.1136/jitc-2021-002754
- Wilhelm, M., Zolg, D. P., Graber, M., Gessulat, S., Schmidt, T., Schnatbaum, K., Schwencke-Westphal, C., Seifert, P., de Andrade Kratzig, N., Zerweck, J., Knaute, T., Braunlein, E., Samaras, P., Lautenbacher, L., Klaeger, S., Wenschuh, H., Rad, R., Delanghe, B., Huhmer, A., . . . Kuster, B. (2021). Deep learning boosts sensitivity of mass spectrometry-based immunopeptidomics. Nat Commun, 12(1), 3346. [open access]. https://doi.org/10.1038/s41467-021-23713-9
- Braunlein, E., & Krackhardt, A. M. (2017a). Identification and Characterization of Neoantigens As Well As Respective Immune Responses in Cancer Patients. Front Immunol, 8, 1702. [review] [open access]. https://doi.org/10.3389/fimmu.2017.01702
- Braunlein, E., & Krackhardt, A. M. (2017b). Tools to define the melanoma-associated immunopeptidome. Immunology, 152(4), 536-544. [review] [open access]. https://doi.org/10.1111/imm.12803
- Bassani-Sternberg, M.*, Braunlein, E.*, Klar, R., Engleitner, T., Sinitcyn, P., Audehm, S., Straub, M., Weber, J., Slotta-Huspenina, J., Specht, K., Martignoni, M. E., Werner, A., Hein, R., D, H. B., Peschel, C., Rad, R., Cox, J., Mann, M., & Krackhardt, A. M. (2016). Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nat Commun, 7, 13404. *Equal contribution [open access]. https://doi.org/10.1038/ncomms13404
Written applications regarding dissertations including CV are welcome and should be forwarded by e-mail to Eva Bräunlein.
- CRC TRR 338 – LETSimmun (Deutsche Forschungsgemeinschaft)
- José Carreras-DGHO-Promotionsstipendium