CAR-T Targeted T Cells News:

[Attitude67]

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[Attitude67]

The simplest way to compare treatments is the survival rate. Provenge confers 4.1 months of increased life expectancy for PCa by boosting immune system response. It was the earliest successful attempt to program T Cells to attack PCa.

CAR-T confers no benefit for PCa at this time because the Human Studies have not yet been completed. There is no increased life expectancy for PCa, however the treatment of Childhood Leukemia has been so successful that similar potentials for each and every cancer type are expected.

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[Attitude67]

What is CAR-T, explanation for health care professionals, and the

patients physicians:

What are CARs?

Chimeric antigen receptors (CARs) are recombinant receptor constructs composed of an extracellular single-chain variable fragment (scFv) derived from an antibody, joined to a hinge/spacer peptide and a transmembrane domain, which is further linked to the intracellular T cell signaling domains of the T cell receptor. CAR specificity for a tumor antigen comes from the extracellular domain. The intracellular domain is designed to replicate the normal series of events by which T cells are activated.1

CAR T cells are investigational cellular biologics that combine CARs with an individual patient’s T cells to redirect T cell specificity to target a tumor-associated antigen in a human leukocyte antigen (HLA)–independent manner.

How does CAR T cell therapy work?

CAR T cell therapy is still in development, but it is designed to recognize tumor-associated antigens on malignant cells and stimulate a T cell antitumor response. CARs can be designed to recognize virtually any antigen on the surface of cells, such as the CD19 or CD22 markers on the surface of B cells. Because CAR T cell therapies recognize tumor antigens independent of HLA and provide their own co-stimulatory signaling, they may have the potential to kill targeted cancer cells that have evolved to escape immune surveillance.

How can CAR T cell therapy kill tumor cells?

The precise mechanism is still under investigation, but CAR T cell therapies are thought to have the ability to recognize and bind to targeted tumor cells independent of HLA. Binding induces a conformational change that leads to intracellular signaling and activation of the T cell. Activated CAR T cells may release cytokines and transcription factors that may promote cell survival and function, and IL-2 that may promote T cell survival. Fas Ligand (FasL) and TRAIL are thought to induce tumor cell apoptosis, and IFN-gamma may activate the innate immune response.

In what tumor types is CAR T cell therapy being studied?

CAR T cell therapies are under investigation for the treatment of CD19-positive B cell malignancies such as acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and diffuse large B cell lymphoma (DLBCL).6 CAR T cell therapy is also under investigation for acute myelogenous leukemia (AML), multiple myeloma, and several solid tumor types.

What is the process for developing and administering CAR T cell therapy?

Development of CAR T cells begins with collection of the patient’s lymphocytes through apheresis. The CAR gene construct is inserted into the genome of the patient’s T cells through activation and transduction. CAR-expressing T cells are expanded, or grown, into a therapeutic dose. After conditioning therapy, the CAR T cells are administered into the patient, and the activated T cells may multiply and provide activity against targeted tumor cells. The patient's healthcare team then monitors the patient for any signs of adverse reactions.

What role does CD4/CD8 composition play in the activity of CAR T cell therapy?

CD4 and CD8 T cells are functionally distinct subsets that differ in their ability to proliferate and persist in the body, and their relative composition may affect the T cell antitumor response. Heavily pre-treated adult patients with B cell malignancies have highly variable numbers and proportions of CD4 and CD8 subsets, with most patients having a higher percentage of CD8 cells and a lower percentage of CD4 cells than normal controls. As part of the manufacturing process for investigational CAR T cell therapies, the subtypes may be separated during purification to adjust their relative composition either before or after expansion. The clinical importance of T cell composition in CAR T cell therapy is under investigation.

What have been the early clinical trial results for CAR T cell therapy?

The early results of CAR T cell therapies for hematologic malignancies have been promising, but the clinical safety and efficacy profiles of these investigational agents will only be established when the results of larger, ongoing trials are available.

The first clinical trial results of CD19-targeted CAR T cell therapy for hematologic malignancies started being reported in 2010. Since then, many additional studies have been published. The potential of CAR T cell therapy has generated considerable excitement due to the rates and duration of complete remission observed in patients with relapsed or refractory disease who had previously received multiple lines of treatment.

A number of CAR T cell investigational agents have received a breakthrough therapy designation from the FDA. A breakthrough therapy designation is for a drug that treats a serious or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on at least one clinically significant endpoint over available therapies.

What toxicities have been associated with CAR T cell therapy in clinical trials?

Serious toxicities, requiring immediate medical attention and sometimes resulting in death, are known to occur with CAR T cell therapy. Reported treatment-related toxicities have been similar across CD19-targeted CAR T trials for hematologic malignancies. They have included cytokine release syndrome (CRS), neurotoxicities, and B cell aplasia, although the incidence and severity of the toxicities has differed across trials.

Further information will be reported as it becomes available.

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Did you copy this from someplace or do you understand all this?

[Attitude67]

CAR-T investigators are close to human studies committee approval for clinical trials. This is information provided for allied health professionals such as myself.

The Principal investigators are required to provide this type of information to allied health professionals if they receive public funding for any of the research being conducted. Many patients here are sophisticated consumers, many are not. All Biomedical information should be discussed with your/their oncologist or your/their urologist with no exceptions. Blog information is no substitute for professional evaluation by a licensed provider.

CAR-T is intended to be Treatment with intent to cure and though it may identify the possibility of many less expensive therapeutic vaccines sometime in the future, it is my opinion that for those that can afford treatment the technology itself may increase survival rates by years rather than months.

As to your personal question I am a graduate of Temple University's undergraduate Honors Program and its School of Social Administration (Health Care Tract).

I did my Administrative Internship at Hahnemann Medical College and University of the Health Sciences where I was Student Assistant to the Director of Social Work Programs, and a member of the University's Human Studies Committee.

Early in my career I was the Director of the Office of Research Administration at Graduate Hospital of the University of Pennsylvania, subsequently becoming an Investigator for the Office for Protection from Research Risk, the Superior Courts of California, and other Courts in the Jurisdictions of the Western United States before retiring.