On this episode of Molecular Moments, Dr. Jim McNally chats with DMPK Senior Director Dr. David Johnson, Ph.D., from BioAgilytix
Tumor diseases are one the most frequent causes of death in Western industrialized countries. Immune oncological approaches are helping to drive new levels of curative cancer treatment, and could possibly even lead to the eradication of most types of cancer, but development of these tools requires specific and sensitive bioanalytical methods and customized oncology assays.
The clinical landscape for cancer is currently undergoing an exciting shift as the spectrum of available medicines has expanded beyond chemotherapy to a host of new molecularly targeted therapies. While in previous years all cell types were targeted by conventional therapeutics, novel drug options are targeting tumor cells only. Whereas drugs conjugated with specific antibodies (ADC, Antibody-Drug conjugates) bring the tumor-killing agent to its location to eliminate tumor cells only, novel immune oncological therapeutic options take advantage of the immune system to eliminate cancer cells.
The treatment of cancer by immunological tools can be tracked back to the early 1900s when Paul Ehrlich brought up the hypothesis that an intact immune system may protect from most cancers. These ideas led to the concept of immunosurveillance by Burnet and Thomas and immunoediting. With the understanding about the enormous diversity of both the humoral and cellular immune system and the recognition that the immunological players exist in all beings, it was a consequent idea to stimulate the immune system leading to a specific killing of cancer cells.
This molecular and possibly personalized approach may lead to the dusk of generic chemotherapies and to a new level of curative cancer treatment and possibly even to the eradication of most types of cancer.
For more information emphasizing associations of ADA development with pharmacokinetics, efficacy, and safety that are necessary to assess the clinical relevance of immunogenicity.
With the increasing average life span of the population, 14 million new cases of cancer worldwide are diagnosed per year. The following examples are intended to demonstrate the immense power of immune oncological treatment options to address these cases, and are not mentioned to be a comprehensive overview nor a specific prioritization.
The first example are monoclonal antibodies which are directed against cancer-specific antigens, e.g. a monoclonal antibody directed against TYRP1, a protein which is highly expressed in melanocytes and melanoma cells. First results are highly promising that advanced malignant melanoma can be treated.
Another example of a promising immunotherapeutic approach are inhibitors of certain lymphocytes surface marker, e.g. NKTR-214 is a CD122 agonist designed to initiate a rapid proliferation of T- lymphocytes and Natural Killer (NK) cells. In addition, this molecule enhances the expression of PD-1 (programmed cell death protein 1) in these immune cells. Results of a Phase 1 study were recently presented at the 2016 annual meeting of the Society for Immunotherapy of Cancer.
Equally promising is the approach which should be paid attention on is the development of agent that interact with intracellular checkpoints such as PD-1 (programmed cell death protein 1) or LAG-3 (lymphocyte activation gene 3).
And finally, a cellular approach is the use of adoptive cell therapy (ACT) by the generation of chimeric antigen receptor T lymphocytes (CAR-T) which utilize patient’s tumor-infiltrating lymphocytes (TIL) to kill their own tumor cells. Novel molecular tools enable the specific design of these transformed cells. This approach widely opens the doors for personalized medicines.
When it comes to immuno-oncology assessments, a broad range of analytical methods across diverse matrices, including tumor, blood, cells, and DNA/RNA, is necessary to paint the best, most informative picture. Options include the measurement of circulating proteins in the blood using immunoassays; the examination of the cellular component of the blood, including the analysis of circulating tumor cells and/or circulating free DNA via flow cytometry; and tumor gene expression by PCR.
Patient samples are precious and are often subject to limited availability — either in terms of the biopsy material available or blood volume restriction. This necessitates highly sensitive and reproducible assays capable of running small sample volumes, such as the multiplex assays described above. Immunoassays and flow cytometry allow more data to be generated from the smallest amount of sample.
The measurement of gene expression is generally performed by quantitative real-time RCR, and multiplex or singleplex ELISpot analysis is applied for the measurement of specific T- or B cell responses. BioAgilytix has all of these platforms as part of our premier bioanalytical technology suite, including:
Explore insights from BioAgilytix Founder and Board Member, Dr. Afshin Safavi, on some of the innovations taking place in the immuno-oncology field, particularly with CAR T therapies, in one of his latest blog posts.
Immune oncological approaches are exciting tools to curatively treat and possibly eradicate cancer. Several humoral and cellular approaches are followed and are in clinical studies. These novel therapeutic tools require specific and sensitive bioanalytical methods and customized assays. On top of this, a clear and distinct clinical evaluation is needed.
BioAgilytix’s veteran scientists are working alongside leading pharma and biotech companies to advance promising immune oncological approaches and tools, from oncology biomarker development to assays for immunogenicity testing, through expert bioanalysis. Let us help you realize the opportunities available in new molecularly targeted therapies for cancer treatment by leveraging our proven, seasoned scientific support.