Prof Misty Jenkins AO, Lab Head | WEHI Researcher Profile

Q: Investigating CAR-pooling as immunotherapy for brain cancer

In this project, we are investigating the rules of engagement for multi-targeted CAR T cells. We are studying the signalling requirements for an effective dual-specific T cells response to cancer, and understanding the trafficking and establishment of memory CAR T cells.

Q: Generating tumour specific CAR T cells for immunotherapy treatment of paediatric diffuse midline glioma and ependymoma

In this project, we have generated novel tumour-specific CAR T cells to treat paediatric glioma and are currently testing these in vitro and in vivo.

Q: Generating tumour specific CAR T cells for immunotherapy treatment of adult glioblastoma

In this project, we have generated novel tumour-specific CAR T cells to treat adult glioblastoma and are currently testing these in vitro and in vivo.

Q: Analysing the tumour immune microenvironment of paediatric and adult brain cancers.

In this project, I aim to define the tumour immune microenvironment of brain cancer using high-throughput spatial technologies such as MIBI-FOF (spatial proteomics) and CosMx (spatial transcriptomics).

About

Our team is focused on a number of projects that investigate cytotoxic CD8+ T cell lymphocyte responses to cancer. Our research aims to understand various aspects of the killing process: the interplay between killer lymphocytes and other immune cells, and the subsequent consequences for the immune system.

Our projects utilise live cell imaging techniques, together with cellular immunology approaches.

Our research focusses on a type of adoptive T cell immunotherapy called Chimeric Antigen Receptor T cell (CAR T cell) therapy. CAR T cells are engineered from a patient’s own T cell, to recognise and attack cancer cells. We are designing and testing CAR T cells directed against adult and paediatric brain tumours. We are also investigating how to best activate T cells to allow for tailored immune responses to solid tumours.

The biological understanding and development of new immunotherapies has undergone a revolution in the past decade. Our research will provide insights into T cell biology and we anticipate that our research will ultimately reveal enhanced strategies for targeting tumour antigens in the brain, to treat patients clinically.

Education

Grants and funding

Publications

Selected publications from Prof Misty Jenkins AO

Dewdney B, Jenkins MR, Best SA, Freytag S, Prasad K, Holst J, Endersby R, Johns TG. From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress. Signal Transduction and Targeted Therapy. 2023;8(1):10.1038/s41392-023-01637-8

Prasad K, Cross RS, Jenkins MR. Synthetic biology, genetic circuits and machine learning: a new age of cancer therapy. Molecular Oncology. 2023;17(6):10.1002/1878-0261.13420

Hansford J, Valvi S, de Boer J, McCowage G, Govender D, Kirby M, Ziegler D, Manoharan N, Hassall T, Wainwright B, Alvaro F, Wood PJ, Eisenstat D, Quang DAK, Jenkins M, Dun M, Laughton SJ, Endersby R, Dodgshun A, Gottardo N. “If you build it, they will come”: the convergence of funding, research and collaboration in paediatric brain cancer clinical trials. The Medical Journal of Australia. 2024;221(10):10.5694/mja2.52506

Lertsumitkul L, Iliopoulos M, Wang SS, McArthur SJ, Ebert LM, Davenport AJ, Endersby R, Hansford JR, Drummond KJ, Cross R, Jenkins MR. EphA3-targeted chimeric antigen receptor T cells are effective in glioma and generate curative memory T cell responses. Journal for ImmunoTherapy of Cancer. 2024;12(8):10.1136/jitc-2024-009486

Davenport AJ, Lertsumitkul L, Cross RS, Jenkins MR. IMMU-10. DEVELOPING NOVEL CHIMERIC ANTIGEN RECEPTOR THERAPIES FOR PAEDIATRIC HIGH GRADE GLIOMA. Neuro-Oncology. 2024;26(Supplement_4):10.1093/neuonc/noae064.381

Jenkins MR, Drummond KJ. CAR T-Cell Therapy for Glioblastoma. New England Journal of Medicine. 2024;390(14):10.1056/nejme2401307

Mehta PH, Trollope GS, Leung P, Chinni SS, Iasinskaia A, Harrison AJ, Hughes‐Parry H, Jenkins MR, Kershaw MH, Jaworowski A, Slaney CY, Koldej RM, Ritchie DS, Quinn KM. Choice of activation protocol impacts the yield and quality of CAR T cell product, particularly with older individuals. Clinical & Translational Immunology. 2024;13(12):10.1002/cti2.70016

Ralalage PB, Mitchell T, Zammit C, Baynam G, Kowal E, Masey L, McGaughran J, Boughtwood T, Jenkins M, Pratt G, Ferdinand A. “Equity” in genomic health policies: a review of policies in the international arena. Frontiers in Public Health. 2024;12:10.3389/fpubh.2024.1464701

Reis ALM, Rapadas M, Hammond JM, Gamaarachchi H, Stevanovski I, Ayuputeri Kumaheri M, Chintalaphani SR, Dissanayake DSB, Siggs OM, Hewitt AW, Llamas B, Brown A, Baynam G, Mann GJ, McMorran BJ, Easteal S, Hermes A, Jenkins MR, Patel HR, Deveson IW. The landscape of genomic structural variation in Indigenous Australians. Nature. 2023;624(7992):10.1038/s41586-023-06842-7

Silcocks M, Farlow A, Hermes A, Tsambos G, Patel HR, Huebner S, Baynam G, Jenkins MR, Vukcevic D, Easteal S, Leslie S. Indigenous Australian genomes show deep structure and rich novel variation. Nature. 2023;624(7992):10.1038/s41586-023-06831-w

Wang SS, Pandey K, Watson KA, Abbott RC, Mifsud NA, Gracey FM, Ramarathinam SH, Cross RS, Purcell AW, Jenkins MR. Endogenous H3.3K27M derived peptide restricted to HLA-A∗02:01 is insufficient for immune-targeting in diffuse midline glioma. Molecular Therapy Oncology. 2023;30:10.1016/j.omto.2023.08.005

Chandler NJ, Davey AS, Elazar A, Weinstein JY, Nguyen JV, Trenker R, Cross RS, Jenkins MR, Call ME, Fleishman SJ, Call MJ. De novo -designed transmembrane domains tune chimeric antigen receptor function. Acta Crystallographica Section A: Foundations and advances. 2023;79(a2):10.1107/s2053273323086722