Biomarker Identifies Melanoma Patients Who May Respond to Immunotherapy MK-3475

“Among melanoma patients treated with the PD-1 inhibitor MK-3475, those whose tumors had the protein PD-L1 had better immune responses and higher survival rates, according to results presented here at the AACR Annual Meeting 2014, April 5-9.

“When the protein PD-L1, which is present on some melanoma tumors, binds to PD-1, a protein present on T cells, “brakes” are applied on these T cells, preventing them from attacking the cancer cells. The immunotherapy MK-3475 blocks PD-1, releasing the brakes on T cells and enabling them to attack the cancer cells.”

Editor’s note: This story is about a drug called MK-3475 (aka lambrolizumab), which boosts a patient’s own immune system to fight cancer. It has shown promising results in clinical trials. Learn more about MK-3475 in this blog post.


Deploying the Body's Army

“More than a century ago, American bone surgeon William Coley came across the case of Fred Stein, whose aggressive cheek sarcoma had disappeared after he suffered a Streptococcus pyogenesinfection following surgery to remove part of the large tumor. Seven years later, Coley tracked Stein down and found him alive, with no evidence of cancer. Amazed, Coley speculated that the immune response to the bacterial infection had played an integral role in fighting the disease, and the doctor went on to inoculate more than 10 other patients suffering from inoperable tumors with Streptococcus bacteria. Sure enough, several of those who survived the infection—and one who did not—experienced tumor reduction.”

Editor’s note: This article is a great overview of immunotherapy for treating cancer. Immunotherapy drugs boost a patient’s own immune system to fight cancer. Learn more.


Deploying the Body's Army

“More than a century ago, American bone surgeon William Coley came across the case of Fred Stein, whose aggressive cheek sarcoma had disappeared after he suffered a Streptococcus pyogenesinfection following surgery to remove part of the large tumor. Seven years later, Coley tracked Stein down and found him alive, with no evidence of cancer. Amazed, Coley speculated that the immune response to the bacterial infection had played an integral role in fighting the disease, and the doctor went on to inoculate more than 10 other patients suffering from inoperable tumors with Streptococcus bacteria. Sure enough, several of those who survived the infection—and one who did not—experienced tumor reduction.”

Editor’s note: This article is a great overview of immunotherapy for treating cancer. Immunotherapy drugs boost a patient’s own immune system to fight cancer. Learn more.


Deploying the Body's Army

“More than a century ago, American bone surgeon William Coley came across the case of Fred Stein, whose aggressive cheek sarcoma had disappeared after he suffered a Streptococcus pyogenesinfection following surgery to remove part of the large tumor. Seven years later, Coley tracked Stein down and found him alive, with no evidence of cancer. Amazed, Coley speculated that the immune response to the bacterial infection had played an integral role in fighting the disease, and the doctor went on to inoculate more than 10 other patients suffering from inoperable tumors with Streptococcus bacteria. Sure enough, several of those who survived the infection—and one who did not—experienced tumor reduction.”

Editor’s note: This article is a great overview of immunotherapy for treating cancer. Immunotherapy drugs boost a patient’s own immune system to fight cancer. Learn more.


New Therapies Targeting Cancer could Change Everything

“In the summer of 2012, a year after his wife had died of lung cancer, Michael Harris scraped open an old mole on his back and it would not stop bleeding. The doctors said he had stage 4 melanoma, with a virtually inoperable tumor, and that patients in his condition typically lived about eight months. By last June, the cancer had spread to his liver and lungs.

“At that point Harris joined a clinical trial at Georgetown University, one of scores that have sprung up around the country to test a new class of cancer drugs called immune-checkpoint inhibitors. Two weeks after his first infusion, Harris’s primary tumor was fading, along with the black cancerous beads around it. A month later, his liver and lungs were clean.”


Immune System-Boosting Treatments Show Long-Sought Successes for Lung Cancer Patients


In the past 2 years, cancer treatments known as immune therapies have become all the rage. However, they have actually been explored for decades, particularly in melanoma, and have produced some notable successes. Now, immune therapies are showing more and more promise for lung cancer. Continue reading…


OX40 is a Potent Immune Stimulating Target in Late Stage Cancer Patients

“OX40 is a potent co-stimulatory receptor that can potentiate T cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function and survival of T cells. Preclinical studies have shown that OX40 agonists increase anti-tumor immunity and improve tumor-free survival. In this study, we performed a Phase I clinical trial using a mouse monoclonal antibody (mAb) that agonizes human OX40 signaling in patients with advanced cancer. Patients treated with one course of the anti-OX40 mAb showed an acceptable toxicity profile and regression of at least one metastatic lesion in 12/30 patients. Mechanistically, this treatment increased T and B cell responses to reporter antigen immunizations, led to preferential upregulation of OX40 on CD4+ FoxP3+ regulatory T cells in tumor-infiltrating lymphocytes andincreased the anti-tumor reactivity of T and B cells in patients with melanoma. Our findings clinically validate OX40 as a potent immune-stimulating target for treatment in cancer patients, providing a generalizable tool to favorably influence the antitumor properties of circulating T cells, B cells and intratumoral regulatory T cells.”


Anti-CCR4 mAb Selectively Depletes Effector-Type FoxP3+CD4+ Regulatory T Cells, Evoking Antitumor Immune Responses in Humans

“Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a critical role in suppressing antitumor immune responses. Here we found that, compared with peripheral blood T cells, tumor-infiltrating T cells contained a higher frequency of effector Tregs, which are defined as FOXP3hi and CD45RA, terminally differentiated, and most suppressive. Effector Treg cells, but not FOXP3lo and CD45RA+ naïve Treg cells, predominantly expressed C-C chemokine receptor 4 (CCR4) in both cancer tissues and peripheral blood. In vivo or in vitro anti-CCR4 mAb treatment selectively depleted effector Treg cells and efficiently induced tumor-antigen-specific CD4+ and CD8+ T cells. Thus, cell-depleting anti-CCR4 mAb therapy is instrumental for evoking and enhancing tumor immunity in humans via selectively removing effector-type FOXP3+ Treg cells.”


Particle Shape Dependence of CD8+ T cell Activation by Artificial Antigen Presenting Cells

“Previous work developing particle-based acellular, artificial antigen presenting cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs (p = 0.004) and cognate spherical aAPCs (p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T cells and biological APCs.”