Immunology and Biotherapies

Abstract

Lung cancer remains the most common cause of cancer-related deaths in the United States, with SEER data showing lung cancer accounting for 29% of all male-related cancer mortality and 26% of all female-related mortality. Patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) who have localized disease both have 5-year survival rates of 52.2%, whereas patients with metastatic disease have 5-year survival rates of only 3.7%. Traditional anti-cancer therapies (surgery, radiotherapy, and chemotherapy) have limited effectiveness in curbing progression. However, advances in immunology and molecular biology in the past two decades have resulted in improved prognosis for those with SCLC and NSCLC, although novel therapies are still needed to make significant improvements in median overall and progression-free survival rates. Notable progress on the importance of tumor immunology has included work on immune surveillance, antigenic targets, and immune checkpoints. Immunotherapies, including vaccines, which can induce antitumor responses by harnessing the power of the immune system, may help to fill this void, and the cancer vaccine continues to be studied as adjunctive therapy. Here, we review recently reported results from clinical trials as well as the possible future roles of vaccine therapy in the treatment of SCLC and NSCLC patients.

Via Krishan Maggon

Abstract

The concept of immunotherapy as a modality to treat cancer was recognized more than a hundred years ago. High-dose interleukin-2 (IL-2) was one of the first agents to demonstrate that the host's immune system can be harnessed to treat even advanced malignancy, as was shown in a subset of patients with renal cancer and melanoma. Many tumours are immunogenic and provoke a host immune response, but this is normally not sufficient to overcome host tolerance. For decades now, researchers have tried various methods to enhance host immunological responses, such as the use of non-specific immunotherapeutic cytokines, tumour vaccines, adoptive immunotherapy and the use of monoclonal antibodies against a wide variety of molecules. This review discusses the principles of the various types of immune therapy and focuses on some of the recent developments and successes in treatment. The article concentrates on the applications of immunotherapy in solid tumours, though it has immense value in haematological cancers.

Via Krishan Maggon

#endcancer
The Promise of #Immunotherapy for the Treatment of #Cancer
http://t.co/tbcOMVhLiD

Via Krishan Maggon

Abstract

Therapeutic cancer vaccines have the potential of being integrated in the therapy of numerous cancer types and stages. The wide spectrum of vaccine platforms and vaccine targets is reviewed along with the potential for development of vaccines to target cancer cell “stemness,” the epithelial-to-mesenchymal transition (EMT) phenotype, and drug-resistant populations. Preclinical and recent clinical studies are now revealing how vaccines can optimally be used with other immune-based therapies such as checkpoint inhibitors, and so-called nonimmune-based therapeutics, radiation, hormonal therapy, and certain small molecule targeted therapies; it is now being revealed that many of these traditional therapies can lyse tumor cells in a manner as to further potentiate the host immune response, alter the phenotype of nonlysed tumor cells to render them more susceptible to T-cell lysis, and/or shift the balance of effector:regulatory cells in a manner to enhance vaccine efficacy. The importance of the tumor microenvironment, the appropriate patient population, and clinical trial endpoints is also discussed in the context of optimizing patient benefit from vaccine-mediated therapy.

Via Krishan Maggon

Abstract

Cancer vaccines are designed to promote tumor specific immune responses, particularly cytotoxic CD8 positive T cells that are specific to tumor antigens. The earliest vaccines, which were developed in 1994-95, tested non-mutated, shared tumor associated antigens that had been shown to be immunogenic and capable of inducing clinical responses in a minority of people with late stage cancer. Technological developments in the past few years have enabled the investigation of vaccines that target mutated antigens that are patient specific. Several platforms for cancer vaccination are being tested, including peptides, proteins, antigen presenting cells, tumor cells, and viral vectors. Standard of care treatments, such as surgery and ablation, chemotherapy, and radiotherapy, can also induce antitumor immunity, thereby having cancer vaccine effects. The monitoring of patients’ immune responses at baseline and after standard of care treatment is shedding light on immune biomarkers. Combination therapies are being tested in clinical trials and are likely to be the best approach to improving patient outcomes.

Via Krishan Maggon

Immunotherapies for cancer are demonstrating increasing success. These agents can amplify existent antitumour immunity or induce durable antitumour immune responses in a wide array of cancers. The spectrum of immunotherapeutics is broad, spanning monoclonal antibodies and their derivatives, tumour vaccines, and adoptive therapies using T cells and natural killer cells.

Only a small number of immunotherapies have been tested in paediatric cancers, but impressive antitumour effects have already been observed. Mononclonal antibodies targeting GD2 that induce antibody-dependent cell-mediated cytotoxicity improve survival in high-risk neuroblastoma. Bi-specific monoclonal antibodies that simultaneously target CD19 and activate T cells can induce remission in acute B-cell lymphoblastic leukaemia (B-ALL) and adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors targeting CD19 induce impressive responses in B-ALL. Efforts are underway to generate and test new immunotherapies in a wider array of paediatric cancers. Major challenges include a need to identify immunotherapy targets on the most lethal childhood cancers, to expand availability of technology-intense platforms, such as adoptive cell therapy, to optimize management of novel toxicities associated with this new class of cancer therapies and to determine how best to incorporate these therapies into standard treatment paradigms.

Via Krishan Maggon

AbstractWe have recently reported that LAG-3 (CD223) mediates the alternative, IFNα-deficient activation of pDCs at tumor sites. Our findings define a novel tumor-driven strategy that promotes immunosuppression by pDCs, and we have provided more detailed information regarding the immunomodulatory role of LAG-3. The translational relevance of our results for the treatment of tumors and autoimmune diseases is discussed herein.

Via Krishan Maggon