Cancer Immunotherapy and Personalized Medicine: Emerging Technologies and Biomarker Based Approaches

Abstract

Purpose of review The vision and strategy for the 21st century treatment of cancer calls for a personalized approach in which therapy selection is designed for each individual patient. While genomics has led the field of personalized cancer medicine over the past several decades by connecting patient-specific DNA mutations with kinase-targeted drugs, the recent discovery that tumors evade immune surveillance has created unique challenges to personalize cancer immunotherapy. In this mini-review we will discuss how personalized medicine has evolved recently to accommodate the emerging era of cancer immunotherapy. Moreover, we will discuss novel platform technologies that have been engineered to address some of the persisting limitations. Recent finding Beginning with early evidence in personalized medicine, we discuss how biomarker-driven approaches to predict clinical success have evolved to account for the heterogeneous tumor ecosystem. In the emerging field of cancer immunotherapy, this challenge requires the use of a novel set of tools, distinct from the classic approach of next-generation genomic sequencing-based strategies. We will introduce new techniques that seek to tailor immunotherapy by re-programming patient-autologous T-cells, and new technologies that are emerging to predict clinical efficacy by mapping infiltration of lymphocytes, and harnessing fully humanized platforms that reconstruct and interrogate immune checkpoint blockade, ex-vivo. Summary While cancer immunotherapy is now leading to durable outcomes in difficult-to-treat cancers, success is highly variable. Developing novel approaches to study cancer immunotherapy, personalize treatment to each patient, and achieve greater outcomes is penultimate to developing sustainable cures in the future. Numerous techniques are now emerging to help guide treatment decisions, which go beyond simple biomarker-driven strategies, and are now we are seeking to interrogate the entirety of the dynamic tumor ecosystem.

Cancer Immunotherapies and Humanized Mouse Drug Testing Platforms

“…Moreover, the concept of personalized precision cancer treatment imposes another obstacle for the treatment option. Due to the heterogeneity of individual’s tumor, tumor microenvironment and the immune system, there is a considerable variation in individual’s responses, including the anti-cancer effects and the side effects towards the same treatment [74]. Therefore, continuous development and improvement of immuno-oncology assay methods are essential to expedite evaluation of single or combinational immunotherapy in cancer research, or predict the clinical outcome of an individual cancer patient.…”

The growing role of precision and personalized medicine for cancer treatment

“…Another class of cancer treatments that have paved the way to more specific and effective therapies is immunotherapy, which harnesses a patients’ own immune system to fight cancer. Immunotherapy treatments include monoclonal antibodies (mAbs), checkpoint inhibitors, cytokines, vaccines, and adoptive cell transfer, most prominently in the form of hematopoietic stem cell transplants (HSCTs) and chimeric antigen receptor (CAR) T-cell therapies 10 . Adoption of immunotherapy has steered the field of cancer treatment toward the concept of precision and personalized medicine (PPM), in which therapy selection is tailored to each individual.…”

Drug Delivery for Cancer Immunotherapy and Vaccines

“…Nearly 1.7 million new cancer diagnoses and 610,000 cancer-related deaths are projected to occur in 2018 in the US alone [1, 2]. Traditional first line treatments for cancer include surgery, chemotherapy, radiation, or a combination of the three [3].…”

“…Traditional first line treatments for cancer include surgery, chemotherapy, radiation, or a combination of the three [3]. However, all of these treatments have drawbacks and relapse can reduce the 5-year survival rate by more than 50% in aggressive cancers [1, 4–6]. Tumor resection is most effective in the early stages of cancer, before metastasis has occurred.…”

“…Immunoediting consists of elimination, equilibrium, and escape phases [8]. During the elimination phase, antitumor responses from the activation of the innate and adaptive immunity occur, but tumor cells that have escaped the elimination phase can continue to proliferate in the equilibrium phase [1, 5, 11, 15]. The escape phase continues with tumor progression and infiltration.…”