CAR-T cells: the long and winding road to solid tumors

[D.ap]

Abstract

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the “next generation” of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host’s defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

* “So Metastatic foci are foci that are metastatic, meaning the cancer cells that can spread to other region of the body, not the cancer cells that are still fixed to its origin *the primary tumour)



https://www.nature.com/articles/s41419-018-0278-6

[D.ap]

“For years, the foundations of cancer treatment were surgery, chemotherapy, and radiation therapy. Over the last two decades, targeted therapies like imatinib (Gleevec®) and trastuzumab (Herceptin®)—drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells—have also cemented themselves as standard treatments for many cancers.

But over the past several years, immunotherapy—therapies that enlist and strengthen the power of a patient’s immune system to attack tumors—has emerged as what many in the cancer community now call the “fifth pillar” of cancer treatment.

A rapidly emerging immunotherapy approach is called adoptive cell transfer (ACT): collecting and using patients’ own immune cells to treat their cancer. There are several types of ACT (see “ACT: TILs, TCRs, and CARs”), but, thus far, the one that has advanced the furthest in clinical development is called CAR T-cell therapy.”

https://www.cancer.gov/about-cancer/tre ... ar-t-cells

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Immunotherapy Offers New Strategy for Treating Sarcoma
View on MSKCC.org
By Jim Stallard Monday, January 22, 2018



“Summary
Soft tissue sarcoma, a diverse group of cancers that arise in the body’s connective tissue, is difficult to treat after it has spread. MSK clinicians are investigating the use of immunotherapy to treat this disease. The main approaches involve checkpoint inhibitors and adoptive T cell therapy, which have shown effectiveness against several other cancers. A few clinical trials have already started at MSK and many more are planned to open soon.

What about the use of adoptive T cell therapy for sarcoma?
We have been collaborating with a company to engineer T cells to fight synovial sarcoma. This type of sarcoma has a specific protein called NY-ESO-1 that is not on other cells. Because of that we are able to target the cancer cells selectively. The treatment is being tested in a pilot study at MSK. The trial involves removing T cells from a person with synovial sarcoma, engineering the cells to recognize the NY-ESO-1 protein, and then giving them back to the person in large numbers.“


https://www.google.com/amp/s/www.mskcc. ... coma%3famp

Discussion of NY-ESO-1 protien in ASPS

http://www.cureasps.org/forum/viewtopic ... SO+1#p9014

[D.ap]

Abstract
NY-ESO-1 (CTAG 1B) is highly expressed in the majority of synovial sarcomas and myxoid/round cell liposarcomas as well as in a subset of melanomas, but only rarely in other mesenchymal tumors. This points to a potential for using NY-ESO-1 in the differential diagnosis of these lesions. Furthermore, promising results have been obtained in clinical trials testing NY-ESO-1-targeted immunotherapy in subsets of melanoma and synovial sarcoma patients.



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518519/