Personalized Vaccines May Hold Promise for Melanoma Treatment

“Personalized melanoma vaccines can be used to marshal a powerful immune response against unique mutations in patients’ tumors, according to early data in a first-in-people clinical trial at Washington University School of Medicine in St. Louis.

“The tailor-made vaccines, given to three with advanced melanoma, appeared to increase the number and diversity of -fighting T responding to the tumors. The finding is a boost to cancer immunotherapy, a treatment strategy that unleashes the immune system to seek out and destroy cancer.

“The research is reported April 2 in Science Express, in a special issue devoted to cancer immunology and immunotherapy.”

INSIGHT-Safety Concerns Cloud Early Promise of Powerful New Cancer Drugs

“A new wave of experimental cancer drugs that directly recruit the immune system’s powerful T cells are proving to be immensely effective weapons against tumors, potentially transforming the $100 billion global market for drugs that fight the disease.

“But top oncology researchers are concerned about the two emerging technologies, citing dangers seen repeatedly in clinical trials including the potentially fatal buildup of toxic debris from killed tumor cells and damage to healthy tissue. Such side effects could block regulatory approval if they aren’t controlled, researchers and drug company executives said in interviews with Reuters.

“In some trials, the two new approaches, known as CAR T cells and bispecific antibodies, have eliminated all traces of blood cancers in 40 percent to 90 percent of patients who had no remaining options. The drugs could reap annual sales in the tens of billions of dollars for their manufacturers, especially if they can also eliminate solid tumors in such terminally ill patients.”

Immune System-Activating Drugs in Combination Treatments May Be Next Big Thing for Melanoma

Among solid tumors, the curative potential of immunotherapies has been explored most in melanoma. One reason for this is that melanoma tumors often contain so-called immune infiltrates—patches of T cells, the killer cells of the immune system. It seems that these fighter cells arrive at the ‘battlefield’ to target tumor cells for killing, but instead become ‘frozen,’ unable to attack.  How to activate the tumor-killing potential of T cells has been an area of intense and fruitful research, leading to the development of several immunotherapy drugs. Continue reading…

Immune System-Boosting Drugs, New and Old, Are Explored in Combination Treatments for Lung Cancer

Readers of this blog will already know a thing or two about immunotherapy (immune system-activating drugs) and targeted therapy in lung cancer. Both approaches have benefited many patients in recent years. Now, research is being done to combine immunotherapies with other types of drugs. Of particular interest are immunotherapies that target PD-1, PD-L1, and CTLA4. These drugs, also known as immune checkpoint antibodies, are being tested in combination with other drugs in patients participating in the clinical trials below. Continue reading…

MacroGenics' DART Candidate IND for Colorectal Cancer, MGD007, Cleared to Start Enrolling Patients

Editor’s note: People with colorectal cancer may soon be able to enroll in a clinical trial to test a new drug called MDG007.

“MacroGenics, Inc. (Nasdaq:MGNX), a clinical stage biopharmaceutical company focused on discovering and identifying innovative monoclonal antibody-based therapeutics for the treatment of cancer and autoimmune diseases, today announced that its investigational new drug (IND) for MGD007 has been cleared by the U.S. Food and Drug Administration (FDA) to proceed with the Phase 1 human clinical trial for this drug candidate. MGD007 is a Dual-Affinity Re-Targeting (DART®) protein being developed for the treatment of colorectal cancer. MacroGenics will receive a $5 million milestone payment from Servier, France’s largest privately-held pharmaceutical company, triggered by the IND clearance.

” ‘MGD007 has demonstrated potent activity in preclinical studies supporting the treatment of colorectal cancer, the second leading cause of cancer-related deaths in the U.S., and an indication for which patients remain underserved despite recent advances in therapies,’ said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. ‘We look forward to initiating the Phase 1 study of MGD007, our second DART candidate to enter the clinic, in the second half of 2014.’

“Under a September 2012 agreement, MacroGenics granted Servier an option to secure an exclusive license to MGD007 in all territories outside North America, Japan, Korea and India. Servier may exercise its option for MGD007 upon MacroGenics’ completion of the Phase 1 trial.”

Two Mutations Linked to Success of Adoptive T-Cell Therapy in Melanoma

“Two novel mutations, KIF2C and POLA2, appeared to be linked to complete cancer regression in two patients with metastatic melanoma who underwent adoptive T-cell immunotherapy, according to study results.

“ ‘This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy,’ Steven A. Rosenberg, MD, PhD, chief of surgery at the NCI, said in a press release. ‘The two targets identified in this study play important roles in cancer cell proliferation.’ ”

Editor’s note: In order to improve new treatments so that more people can benefit from them, it is useful to figure out why they are particularly successful for certain patients. In this story, researchers wished to know why two people with metastatic melanoma experienced complete disappearance of their tumors in response to a treatment called adoptive T-cell transfer. In adoptive T cell transfer, immune system cells are collected from either the patient’s tumor or the blood supply near the tumor. In the laboratory, these cells are multiplied to produce high numbers of ‘killer’ T cells, which are then infused back into the patient, where they are able to recognize and attack cancer cells. It was found that the two patients with exceptionally good responses had two genetic mutations in their tumor cells that the T cells were able to attack directly. The discovery could help researchers learn how to make adoptive T cell transfer more effective for more people.

Astrazeneca’s Medimmune Presents Encouraging Immunotherapy Data at ASCO 2014

“MedImmune, the global biologics research and development arm of AstraZeneca, presented results today from its novel investigational immunotherapy portfolio, focusing on MEDI4736, at the American Society of Clinical Oncology (ASCO) 2014 Annual Meeting.  Overall, studies demonstrated durable clinical activity and tolerability for MEDI4736 across a range of tumor types.

“This announcement follows the recent progression of the first Phase III study for MEDI4736, an investigational, engineered, human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. It is believed that by targeting PD-L1, MEDI4736 may block this ligand from sending out signals to T-cells to ‘ignore’ tumor cells, thereby countering cancer’s immune-evading tactics.

Editor’s note: Immunotherapy treatments that boost a patient’s own immune system to fight cancer are a promising area of cancer research. A new immunotherapy drug called MEDI4736 is being tested in volunteer patients with different cancer types, and has shown good results for some patients with advanced non-small cell lung cancer (NSCLC).

Celldex Therapeutics' Varlilumab Continues to Demonstrate Very Favorable Profile

“Celldex Therapeutics, Inc. (Nasdaq:CLDX) today reported data from its ongoing Phase 1 study of the fully human monoclonal antibody varlilumab (CDX-1127) in cancer. Varlilumab is an immunotherapy designed to enhance the body’s natural immune response by directly activating T cells that can specifically recognize and kill cancer cells. Preclinical data support the broad study of varlilumab in combination with a number of other anti-cancer agents including but not limited to checkpoint inhibitors, chemotherapies, targeted therapies and vaccines. Varlilumab will enter at least four combination studies in the second half of 2014.”

Editor’s note: As mentioned above, varlilumab is an immunotherapy that works by boosting a patient’s own immune system to fight cancer. In a clinical trial testing the drug in volunteer patients, it shown promise for treating several different types of cancer, including metastatic melanoma.

T-cell Changes: Why Only Some Respond to Ipilimumab

“The immunotherapy ipilimumab (Yervoy, Bristol-Myers Squibb Company) works amazingly well in some patients, hardly at all in others. A groundbreaking study that used deep sequencing techniques offers some clues as to why.

“Ipilimumab, which is marketed for melanoma but is being explored in several other cancer types, including prostate cancer, acts as a checkpoint blocker by inhibiting cytotoxic T lymphocyte– associated antigen–4 (CTLA-4).

“Immune repertoire sequencing has confirmed that blocking CTLA-4 increased turnover and diversity of the T-cell repertoire in some patients with advanced prostate cancer or metastatic melanoma, but also showed that patients who survived longest maintained clones of high-frequency T-cells they had developed before starting treatment.”

Editor’s note: Ipilimumab is a drug that boosts a patient’s own immune system to fight cancer. It works by activating immune system cells called T cells, some subtypes of which may then attack tumors. Ipilimumab works very well for some patients, but not for others. This study found that patients who had certain tumor-fighting T cell subtypes already present before ipilimumab treatment were more likely to respond well and survive longer, possibly because these cells were readily available to fight cancer upon activation. The study also found that ipilimumab may prompt the immune system to “re-shuffle” the body’s T cell subtypes, allowing patients with only a small amount of tumor-fighting T cells to generate more. (This may explain why some patients take longer to respond to ipilimumab than others; their immune systems need more time to build up the right T cells.) Based on the results, doctors may be able to monitor a patient’s T cell subtypes (“immune repertoire sequencing”) to determine whether ipilimumab will work, or to keep tabs on the effectiveness of ongoing ipilimumab treatment.