City of Hope is rated No 11 cancer research hospital in the USA.....and No 1 in the west of America.
It some respects, I would value information direct from City of Hope, ahead of that of the company itself. (Although updates and anything at all from CHM is of course, most welcome)
Here is an abstract from City of Hope, presented at AACR in April 2021. In conjunction with GBM studies.....once again we hear from City of Hope,
about CAT T in cancer solid tumors. CAR T is a cancer immunotherapy - as are vaccines, such as those under study at IMU. The implications for success with this companies drug, in "other cancers" ......would hardly be possible to measure in terms of its SP.
Look for news hopefully of additional Clinical Trials, other than GBM.....coming from City of Hope, than see how the SP goes. I think its a real possibiity.
---------This from a recent post........HER2, EphA2 or EGFR are not GBM mutations.CLTX-CAR TThe so-called CLTX-CAR T was deployed at glioblastoma resections in the City of Hope Medical Centre in Los Angeles (USA). It became clear that the CLTX-CAR T bound to a large spectrum of glioblastoma cells.
It did so more than other CAR T cell therapies that are currently being considered, such as those using the antigen IL13Rα2, HER2, EphA2 or EGFR.____________________________________________________________
And what follows is that AACR April abstract
"These studies establish that CAR T cell therapy has the potential to re-shape the tumor microenvironment, creating a context permissible for eliciting endogenous antitumor immunity and emphasize the importance of the host innate and adaptive immunity in productive CAR T cell therapy of solid tumors."---------------------------------------------------------------------
Program Planner Home Print Page Share Page
Session MS.IM02.01 - Adoptive Cell Therapies: Targeting Solid Tumors59 - CAR T cell therapy reshapes the tumor microenvironment to promote host antitumor immune responses in glioblastoma | Column 1 | Column 2 |
|---|
| 1 | April 12, 2021, 2:05 PM - 2:15 PM | Channel 03 |
|---|
Authors
Christine E. Brown,
Darya Alizadeh,
Vanessa Jonsson,
Jonathan Hibbard,
Stephanie Yahn,
Robyn A. Wong,
Xin Yang,
Rachel Ng,
Natalie Dullerud,
Madeleine Maker,
Sharahreh Gholamin,
Renate Starr,
Nicholas Banovich,
Stephen J. Forman,
Behnam Badie. Beckman Research Institute of City of Hope, Duarte, CA, Translational Genomics Research Institute, Phoenix, AZ, University of Southern California, Los Angeles, CA
Disclosures
C.E. Brown: ; Mustang Bio.. ; California Institute for Regenerative Medicine. ; National Cancer Institute.
D. Alizadeh: None.
V. Jonsson: None.
J. Hibbard: None.
S. Yahn: None.
R.A. Wong: None.
X. Yang: None.
R. Ng: None.
N. Dullerud: None.
M. Maker: None.
S. Gholamin: None.
R. Starr: None.
N. Banovich: None.
S.J. Forman: ; Mustang Bio.
B. Badie: ; National Cancer Institute.
Abstract
CAR T cell therapy is emerging as a promising strategy to treat cancer and may offer new therapeutic options for individuals diagnosed with glioblastoma (GBM) and other solid tumors. While early clinical studies evaluating CAR T cell therapy in GBM have established evidence of safety and bioactivity, objective clinical responses have been limited. It remains unclear whether productive CAR T cell therapy for solid tumors requires solely CAR T cell engagement with tumor antigen, or if it also necessitates the stimulation of a patient's endogenous immune response. Focusing on our preclinical and clinical program evaluating IL13Rα2-targeted CAR-T cells for the treatment of IL13Rα2-positive glioblastoma (GBM), we set out to mechanistically interrogate the interplay between CAR T cell therapy and the host tumor microenvironment. We designed a murine CAR T cell syngeneic platform in C57BL/6 immunocompetent mice and demonstrate that single intratumoral infusion of IL13Rα2-CAR T cells mediate potent antitumor activity against established KR158 tumors, a highly invasive and poorly immunogenic murine glioma model. We demonstrate that CAR T cell treatment of mouse syngeneic GBM alters the tumor immune landscape, activates intratumoral myeloid cells and induces endogenous T cell memory responses coupled with feed forward propagation of CAR T responses. IFNγ production by CAR T cells and IFNγ-responsiveness of host immune cells is critical for tumor immune landscape remodeling to promote a more activated and less suppressive tumor microenvironment. The clinical relevance of these findings was explored in patient samples from our on-going IL13Rα2-CAR T cell phase I clinical trial [NCT02208362]. Consistent with our preclinical findings, we show that locoregional CAR T cell infusions result in spikes in inflammatory cytokines and an influx of endogenous immune cells into the cerebrospinal fluid (CSF) and resected tumor cavity. Single cell RNA-sequencing revealed unique genes upregulated in immune cells from blood and CSF samples after treatment. One patient of particular interest, who presented with recurrent multifocal GBM, remarkably achieved a complete response (CR) following locoregional delivery of IL13Rα2-CAR T cells, despite heterogeneous IL13Rα2 tumor expression (PMID: 28029927). In this responding patient, we now show the induction of endogenous tumor-specific T cell reactivity and T cell clones whose dynamics contracted with tumor volume following IL13Rα2-targeted CAR T therapy.
These studies establish that CAR T cell therapy has the potential to re-shape the tumor microenvironment, creating a context permissible for eliciting endogenous antitumor immunity and emphasize the importance of the host innate and adaptive immunity in productive CAR T cell therapy of solid tumors.
(20min delay)