First-in-Human CRISPR Immunotherapy Would Target PD-1

Excerpt:

“At a time when PD-1 inhibitors are dominating the immunotherapy field, a team of researchers is seeking to use groundbreaking CRISPR gene editing technology for the first time in human beings to create an engineered T-cell agent that would knock out the gene that controls the immune checkpoint’s activity.

“Plans for the complex therapy call for taking NY-ESO-1, a peptide-based form of adoptive immunotherapy already in clinical trials, and disrupting the activity of the PDCD1 gene that encodes PD-1 as well as the endogenous TRAC and TRBC genes, which control T-cell receptor (TCR) alpha and beta, respectively.

“The goal would be to enhance the immune response with NY-ESO-1 by eliminating genomic drivers that hamper T-cell proliferation and function, University of Pennsylvania (UPenn) researchers said in describing the proposed study before a National Institutes of Health (NIH) panel on June 21.”

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Merck Extends Cancer Immunotherapy Reach to First-Line Lung Cancer

Excerpt:

“Merck’s (MRK) flagship cancer immunotherapy Keytruda delayed the re-growth of tumors and prolonged survival in patients with newly diagnosed non-small cell lung cancer compared to chemotherapy, the company said Thursday.

“The new phase III study results from Merck are significant because they represent the first time that a drug belonging to the so-called checkpoint inhibitor class of cancer immunotherapies has demonstrated superiority over standard of care in the treatment of first-line lung cancer patients.

“Lung cancer is the most prevalent cancer globally, with more than 200,000 patients in the U.S. and 1.5 million patients globally diagnosed each year. As such, lung cancer is an important commercial market for the drug companies developing new therapies which harness the immune system to target and kill cancer cells.”

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Total Body Irradiation Did Not Improve Response of Adoptive Cell Transfer

Excerpt:

“Adding total body irradiation to preparative lymphodepletion chemotherapy prior to the adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) had no effect on tumor regression in patients with metastatic melanoma, according to the results of a study published in the Journal of Clinical Oncology.

“However, adoptive cell transfer of TILs did mediate the objective complete response of 24% of patients.

“ ‘The nonmyeloablative chemotherapy regimen thus seemed to provide sufficient lymphodepletion for successful adoptive transfer without the need to add total body irradiation,’ wrote researchers led by Stephanie L. Goff, MD, of the National Cancer Institute.”

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Distinct Features Associated With Benefit for BRAF/MEK Inhibition

Excerpt:

“With the development of novel targeted and immunotherapeutic agents that are more efficacious than traditional chemotherapy, treatment paradigms in melanoma have undergone major changes. Current recommendations for first-line systemic therapy for patients with advanced or metastatic melanoma consider BRAF mutation status, tumor growth rate, and the presence or absence of cancer-related symptoms.

“Immunotherapies with agents that block CTLA-4 or PD-1/PD-L1 checkpoints have been associated with durable responses in a subset of patients, and are often considered for patients with low-volume, asymptomatic metastatic melanoma. Targeted therapies, on the other side, are preferred for patients with BRAF-mutant tumors who have symptomatic disease and benefit from the rapid response associated with these agents.”

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A Treatment Vaccine for Low-Risk Prostate Cancer

Excerpt:

“A Louisiana-based biopharmaceutical company is betting that its experimental immunotherapeutic vaccine can keep previously untreated prostate cancer in check.

“The company, OncBioMune Pharnaceuticals, Inc, in Baton Rouge, is planning to test the vaccine, dubbed ProscaVax, in a phase 2 trial for patients with previously untreated prostate cancer and in a second trial for patients with recurrent or hormone-refractory disease.

“The trial of a treatment vaccine in untreated, low-risk prostate cancer patients is novel.”

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Pfizer Cancer Drug Shows Promise in Combo With Merck's Keytruda

Excerpt:

“An experimental Pfizer drug that helps the immune system fight cancer showed early promise against a variety of cancers when used with Merck & Co’s immunotherapy Keytruda in a small clinical trial, according to data released on Wednesday.

“The first wave of successful cancer immunotherapies, such as Keytruda, block mechanisms that tumors use to evade the immune system. Pfizer’s utomilumab, which targets an antibody known as 4-1BB, stimulates a more intense immune system attack. The Pfizer drug has already shown encouraging early results against a form of blood cancer when used with Roche’s Rituxan.

“Researchers are hopeful that combining the two approaches, one that takes the brakes off of the immune system with one that hits the accelerator, will offer long-lasting protection against cancer without adding serious side effects.”

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Immune Drug for Deadly Skin Cancer Shows Long-Term Survival

Excerpt:

“A new kind of drug for the deadliest form of skin cancer helped some patients survive for at least three years, a study shows. It’s a remarkable advance for patients who until recently faced dismal chances of living for more than a few months.

“About 40 percent of melanoma patients in the study were still alive three years later. The drug, which targets the immune system, was used to treat formerPresident Jimmy Carter, who was diagnosed last summer with melanoma that had spread to his brain.

” ‘This is incredible,’ Dr. Caroline Robert, the study’s lead author, said of the results released Wednesday. ‘I spend my time telling my residents that these patients would be dead if it was five years ago.’ ”

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Long-Term Survival Achieved in Metastatic Melanoma With Personalized Vaccine

Excerpt:

“Two patients with melanoma that had spread to the liver survived for at least 8.5 and 12 years after resection of the hepatic tumor and treatment with patient-specific immunotherapeutic vaccines. The vaccines, designed to activate the immune system against the tumor, were derived from the patients’ own dendritic cells loaded with proteins isolated from their tumors, as described in an article published in Cancer Biotherapy and Radiopharmaceuticals.

“Robert O. Dillman, MD, formerly Vice President Oncology, Caladrius Biosciences, Inc. and currently Chief Medical Officer, NeoStem Oncology (Irvine, CA) and Executive Medical and Scientific Director, Hoag Cancer Institute (Newport Beach, CA) discusses the typically poor prognosis for patients with melanoma of the eye or skin that spreads to the liver, and reports on the potential to achieve long-term survival without disease progression in a subset of patients using the eltrapuldencel-T vaccine. One patient had no disease progression for more than 4.5 years, while the other patient survived and remained disease-free for more than 12 years.”

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Understanding the Future of Immunotherapy in Melanoma

Excerpt:

“While there have been many recent advances in the field of melanoma regarding immunotherapy, there is much more is to come, says Antoni Ribas, MD, PhD.

“One notable breakthrough, which demonstrates the significant potential of the field, is the phase II CheckMate-069 trial, which examined the combination of ipilimumab (Yervoy) and nivolumab (Opdivo). The combination showed a 42% improvement in overall survival (OS) when compared with ipilimumab as a monotherapy.

“In an interview with Targeted Oncology, Ribas, a professor of Medicine, Surgery, and Molecular and Medical Pharmacology at the University of California, discusses what these data mean and where the field of immunotherapy in melanoma is headed.”

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