Cellular Therapies in Cancer

In this series, we provide our readers with the latest updates in the field of cellular therapies besides hematopoietic stem cell transplantation (HSCT). Various strategies for adoptive immunotherapy have been developed using a variety of lymphocytes. A vast majority of these involve αβ T cells or natural killer (NK) cells, though γδ T cells and invariant NK-like T cells (iNKT) cells are also been explored. One of the major distinguishing features of these therapies is whether or not the effector cells undergo genetic modification prior to infusion. In the absence of genetic alteration, the use of conventional T or NK cells requires ex vivo expansion/activation to generate sufficient numbers of activated cells, followed in some cases by further in vivo cytokine stimulus to support persistence. Moreover, the conventional effector cells are polyclonal and not entirely antigen specific. Genetic modification imparts antigen-specificity to the cells, which then bind to the target cells with a higher affinity. Examples of such novel approaches include the genetically engineered T cell receptor (TCR) cells or chimeric antigen receptor (CAR) αβ- or γδ- T cells. Although the use of TCR-modified T cells has been limited mostly to treat solid tumors, therapies with CAR αβ T cells have shown tremendous success, especially in patients with high risk CD19 B-cell malignancies. Similarly, genetic modification of NK cells to create CAR-NK cells and the bispecific- and trispecific killer cell engagers (BiKEs/TriKEs) is also being implemented.

The source of effector cells is another factor that classifies adoptive immunotherapy into two broad categories. As allogeneic T cells can cause potentially fatal graft-versus host disease (GVHD), T cell-based adoptive immunotherapy almost always involves autologous cells. On the other hand, as the earlier trials of autologous NK cell therapies were disappointing and because NK cells do not cause GVHD, most of the NK cell immunotherapy trials are harvesting the cells from an allogeneic source.

With the depth of cellular therapies and the emerging cutting edge technology, this comprehensive review intends to provide an overview of its expansive applications.

This series intends to cover the advancements in the field of adoptive immunotherapy focusing on the following topics:
• Cellular therapies using αβ T cells
• Cellular therapies using γδ T cells
• Virus-specific T cells
• Cellular therapies using NK cells
• Cellular therapies using iNKT cells
• Genetically modified T cells, including CAR T cells and TCR-modified T cells
• Genetically modified NK cells, including CAR NK cells, BiKEs/TriKEs and iPSC-derived NK cells