Functional cloning of antibody genes became possible with the availability of a simple system for expressing antibody fragments such as scFv, Fab etc. in soluble form in E.coli. PCR amplified sequences can be assembled as scFv or Fab and cloned into expression vectors to isolate functional clones. Efficient screening method for display of antibody fragments on surface of bacteriophages, which also exploits the correct periplasmic folding of antibodies during phage biosynthesis helps isolate specific antibody fragments. The systematic use of phage display and whole domain randomization to obtain better folding scFv fragments can be used further for obtaining purified antibody fragments in large amounts using multi-step chromatographic purification procedure.Antibodies came to be used in almost all branches of biology, in laboratories, in biotechnology (e.g. biosensors and affinity chromatography), in chemical catalysis, tumor medicine, tissue targeting etc. However, for many applications, only the antigen-binding domains of antibody were required and the rest of the protein was unnecessary or even deleterious.
Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered.The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.