“Glioblastoma is the most common brain tumor in humans and also one of the most difficult cancers to treat; patients with this type of cancer only survive about one year from time of diagnosis. Researchers at Baylor College of Medicine, Texas Children’s Cancer Center, and the Center for Cell and Gene Therapy at Baylor, Texas Children’s Hospital and Houston Methodist are investigating a new treatment option using modified T cells with anti-tumor properties with the goal of improving outcomes for patients with glioblastoma.
Their research focuses on engineered T cells that target the protein HER 2 expressed in low levels in glioblastoma cells. Results of a Phase 1 study published in the current issue of JAMA Oncology established the safety of these HER 2-specific, chimeric antigen receptor modified T cells (CAR T cells) when infused in to patients in increasing doses and, importantly, results also showed a clinical benefit to patients.”
New targeted and immunotherapy drugs have changed the diagnosis of metastatic melanoma from a death sentence into a disease that can potentially be managed and even cured. Nevertheless, these new drugs do not work in all patients, or they may stop working after a transient response. This post (part one of two) will describe ongoing efforts to find drug combinations with higher efficacy than single drugs and decipher the mechanisms underlying drug resistance. Continue reading…
“Determining the next step for a patient with melanoma who has failed or is not a candidate for existing targeted therapies or immunotherapies can be a challenge.
“However, there is hope, says Omid Hamid, MD, chief of Translational Research and Immunotherapy, and director of Melanoma Therapeutics at The Angeles Clinic.
“ ‘There are times when you throw your hands in the air and say, “I’ve run out of options,” ‘ he says. ‘But, all you need to do is look in another direction, open another cabinet, and realize that there are a ton of new options for our patients. These are nontraditional agents that maybe would not come to mind, but can be very effective in first-line, second-line, or any line.’
“Currently, several new checkpoint inhibitors and costimulatory molecules are being explored. These include those that target glucocorticoid-induced tumor necrosis factor receptor (GITR)—which is expressed on CD4- and CD8-positive T cells—in addition to T-regulatory cells, NK cells, and dendritic cells.”
“Recurrence of HER2-positive breast cancer after treatment may be due to a specific and possibly cancer-induced weakness in the patient’s immune system—a weakness that in principle could be corrected with a HER2-targeted vaccine—according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Results of the study show that T cells from patients whose breast cancer had recently recurred showed far weaker response to the HER2 receptor protein, compared to T cells from patients whose breast cancer had not recurred over a long period following treatment. The study, published in JAMA Oncology this week, suggests that patients with HER2-positive breast cancer—which accounts for roughly 20 percent of the 260,000 invasive breast cancers diagnosed in the US each year—might someday undergo immune status monitoring with blood tests before, during and after treatment, to allow physicians to gauge the risk of recurrence, and possibly to reduce that risk with therapies that boost anti-HER2 immunity.”
Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…
It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…
The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…
“Combined treatment with the T-cell checkpoint pathway inhibitors nivolumab and ipilimumab produced significantly higher rates of response and progression-free survival among patients with advanced melanoma (regardless of BRAF mutation status) than did treatment with ipilimumab alone, according to the phase I results of a trial published in the New England Journal of Medicine and presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting.
“ ‘On the basis of the high degree of tumor reduction in the current study, with a high rate of complete responses, a favorable clinical benefit can be anticipated with longer follow-up,’ wrote study author F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute, and colleagues.
“The phase I dose-escalation study included 142 patients with treatment-naive metastatic melanoma. Patients were randomly assigned 2:1 to ipilimumab 3 mg/kg with nivolumab 1 mg/kg or placebo every 3 weeks for four doses, followed by nivolumab 3 mg/kg or placebo every 2 weeks.
“In patients with BRAF wild-type tumors, combined treatment resulted in an objective response rate of 61% compared with 11% in those assigned ipilimumab alone (P < .001). Complete responses occurred in 22% of patients assigned to the combined immunotherapy treatment and none of the patients assigned to monotherapy.”
“A first-in-class immunotherapy called IMCgp100 yielded durable responses in patients with advanced cutaneous melanoma and those with advanced ocular melanoma, according to data from a phase I/IIa clinical trial presented here at the AACR Annual Meeting 2015, April 18-22.
” ‘IMCgp100 is a new type of immunotherapy that has two functional ends,’ said Mark R. Middleton, MD, PhD, professor of experimental cancer medicine at the University of Oxford in the United Kingdom. ‘The targeting end attaches to melanoma cells and the effector end locks on to any neighboring killer T cell [a type of immune cell], resulting in directed destruction of the tumor. One can think of IMCgp100 as a molecular bridge connecting melanoma cells with killer T cells, encouraging the killer T cells to destroy the melanoma cells.
” ‘Last year at the AACR Annual Meeting, we reported the results of the phase I dose-escalation portion of the clinical trial, which showed that IMCgp100 was well tolerated and had efficacy in some patients with advanced melanoma,’ continued Middleton. ‘This year, we are reporting data from 17 patients treated with the maximum tolerated dose of 600 nanograms of IMCgp100 per kilogram or an absolute dose of 50 micrograms of IMCgp100 as part of the phase I and phase IIa portions of the trial.’ “