Enhanced Recognition and Treatment of Solid Tumors

By defining highly specific combinatorial antigen signatures, we can safely target a range of solid tumors with synNotch CAR circuit T cells.
Enhanced Recognition and Treatment of Solid Tumors

Chimeric antigen receptor (CAR) T cells have shown unprecedented clinical efficacy for certain subtypes of B cell malignancies by targeting lineage-specific antigens. The same approach has proved limited for solid tumors where candidate antigens often lack true tumor-specificity, leading to a high risk for on-target/off-tumor toxicities. Through collaborative efforts we have defined new combinatorial antigen signatures that allow for highly tumor-specific and safe targeting of a range of solid tumorsa through the use of synNotch CAR circuit T cells. We continue to define and validate new clinically relevant antigen expression patterns in order to offer cutting-edge therapeutic alternatives for patients with intractable tumors.

While tumor-specific tailored T cells limit the cytotoxic response to the tumor, it is unclear whether a sole CAR-driven response is sufficient to combat the plethora of functional challenges presented to engineered T cells within solid tumors. In addition to defined local expression of a CAR, synNotch circuits offer the ability for an accompanying delivery of a wide range of therapeutic payloads. Through the use of disease relevant syngeneic mouse models with a fully intact immune system, we are now identifying key deliverables for robust rewiring of previously immunosuppressive tumor microenvironments.  Control and understanding of these elements are critical steps in our efforts to enhance the therapeutic efficacy and persistence of engineered T cells and other endogenous immune cells.

Press: Fierce BiotechNew Scientist

Selected Publications

SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models.
Sci Transl Med. 2021 Apr 28;13(591):eabd8836. doi: 10.1126/scitranslmed.abd8836. PMID: 33910981.
Paving New Roads for CARs. Trends Cancer.
2019 Oct;5(10):583-592. doi: 10.1016/j.trecan.2019.09.005. Epub 2019 Oct 19. PMID: 31706506.

Research Team

Axel Hyrenius-Wittsten, Ph.D.
Axel Hyrenius-Wittsten, Ph.D.

Postdoctoral Fellow

Julie Garcia
Julie Garcia

PhD Student

Josef Alavi
Josef Alavi

Staff Research Associate

Nate Perry, M.S.
Nate Perry, M.S.

Staff Research Associate

Garrett Montgomery, M.S.
Garrett Montgomery, M.S.

Lab Manager, Assistant Specialist III

News

Media highlights of Kole and the lab’s research.
'Smart' immune cells kill tumours and stop them regrowing in mice
Read More >>
Attacking glioblastoma and other solid tumors with CAR-Ts that target multiple antigens
Read More >>
Tweaking Mother Nature, biologists aim for better cancer-fighting cells
Read More >>
'Cell Bots' Chase Down Cancer, Deliver Drugs Directly to Tumors
Read More >>
Synthetic Notch receptors were featured in Notable Advances 2016
Read More >>
Kole Roybal receives the inaugural Sartorius & Science Magazine Prize in Regenerative Medicine and Cell Therapy 2018
Read More >>
Boosting the immune system to fight cancer
Read More >>
Cell Design Labs, Little Partner Of Kite Pharma, Pushes T-Cell Engineering Frontier
Read More >>