CAR-T cell Immunotherapy and PD- 1 treatment showed Remarkable Antitumor Activity with no Toxic Effects, An Update on the Ongoing Clinical Trials.

Ongoing clinical trials (May 2015 till April 2020) on CAR- T cell (chimeric antigen receptors) therapy combined with PD-I to specifically target the highly expressed mesothelin (MSLN) protein on the cancer cells has shown promising antitumor activity and is proved to be safe and free of toxic side effects for the mesothelioma patients.

A team of researchers led by Dr. Prasad S. Adusumilli at the Memorial Sloan Kettering Cancer Center, New York, is conducting a study on the development of the clinical procedure targeting mesothelin (MSLN) surface protein.

Experts presented the latest update on these clinical trials on June 4 at the Clinical Science Symposium in ASCO Annual Meeting 2019.

Phase I clinical trial is conducted to check the side effects, safety, dosage, and timing for the application of this treatment. This phase of the study is not designed to cure cancer.

Two Way Approach to Target Mesothelin Protein

The mesothelin protein highly targeted by doctors for treatment in mesothelioma cancers, including malignant pleural mesothelioma.

Researchers were looking for different clinical approaches to strengthen the human immune system, thus to recognize and specifically target mesothelin. Because targeting mesothelin is attacking tumor cells displaying this protein that evidences the presence of mesothelioma.

This clinical approach aims to target mesothelin protein on the cancer cells by combining the CAR-T cell immunotherapy and PD- 1 therapy.

In CAR T-cell therapy, clinically engineered T cells from the patient's immune system are infused by scientists back into the bloodstream. These modified T cells are programmed to target and attack mesothelin containing tumor cells.

PD-1 inhibitors prohibit the tumor cells from blocking the activity of immune cells (engineered T cells). Both these therapies elevate the patient's immune system against MSLN expressing cancers.

A combination of these therapies has shown promising results in the previous results provided by this research team.

In this trial, 20 patients (18 malignant pleural mesothelioma- MPM, one lung cancer, and one breast cancer patient) suffering from MSLN- expressing pleural tumors were included.

14 out of 18 MPM patients received PD-1 treatment along with CAR T-Cell immunotherapy. While remaining patients received MSLN CAR T-cells with CASP-9 safety gene.

This two-way approach provides a unique and targeted method to attack aggressive tumors.

Latest Update Showed Positive Outcome

This ongoing study on devising a treatment for MSLN expressing cancers including mesothelioma began on May 2015 and is intended to complete in April 2020.

Head investigator of the study, Dr. Prasad S. Adusumilli, the deputy chief of thoracic service and co-director of the mesothelioma program at Memorial Sloan Kettering in New York submitted the latest update on this study at the annual ASCO (The American Society of Clinical Oncology) meeting in Chicago.

In a recent update of phase I clinical trial of the CART -cell therapy and PD-1, the researchers observed no toxicities in the patients.

The researchers wrote,

"No CAR T-cell–related toxicities higher than grade 1 were observed. Intense monitoring for on-target, off-tumor toxicity by clinical (chest or abdominal pain), radiological (CT/PET or echocardiogram for pericardial effusion, ascites), laboratory (troponin elevation), and EKG evaluation found no evidence of toxicity. "

Dr. Prasad shared that the PET scan did not detect any active tumor in two patients at the time of the scan. The failure to detect means that no metabolically active metastatic cancer cells were detected. Some doctors describe this as the complete remission of cancer.

Promising Future Aspects of the Treatment

Alongside these remarkable results of two stable patients, five patients showed partial response to this treatment, and four experienced stable tumors for up to 31 weeks of follow up checkup.

However, the average survival time of malignant pleural mesothelioma patients is approximately 12 months, so the efficacy of any treatment to narrow down the tumor growth or stop it from metastasis is an incredible finding. These results are a ray of hope in developing new mesothelioma treatments.

The researchers concluded,

"Intrapleurally administered MSLN-targeted CAR T cells were safe. Encouraging antitumor activity of MSLN-targeted CAR T-cell therapy was observed when combined with anti-PD1 therapy and shows promise for the future development of this approach."

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