Allogeneic Cell Therapy: From Origins to Future Innovations 

The Genesis of Allogeneic Cell Therapy: 

When it comes to cancer treatment, allogeneic cell therapy is nothing short of revolutionary. Stemming from the concept of hematopoietic stem cell transplantation presented 60 years ago, it opened doors to innovative treatments for various diseases, especially leukemia. However, challenges arose, like graft versus host disease (GVHD) and regimen-related toxicities. Authors Yoshiki Furukawa, Yasuharu Hamano, and their team guide us through the history, trials, and tribulations of this therapy and shed light on exciting advances on the horizon. 



Addressing the Challenges: 

GVHD, where donor cells recognize the recipient as foreign and attack, remains a daunting hurdle. The skin often becomes the battleground, affecting up to 75% of chronic GVHD patients. Furthermore, after transplantation, many patients face severe immunodeficiency, making them susceptible to viruses like Cytomegalovirus and Epstein-Barr virus. The delicate balance here is enhancing graft versus leukemia (GVL), which effectively combats leukemia, while minimizing GVHD’s harmful effects. Solutions like donor lymphocyte infusion (DLI) have been explored, but with mixed outcomes. 


The iPSC Revolution: 

In recent years, the discovery of induced pluripotent stem cells (iPSCs) and the advent of CRISPR/Cas9 gene editing have reignited hope for advancing allogeneic cancer immunotherapy. By using iPSC technology, it’s possible to create unlimited allogeneic cytotoxic T lymphocytes, offering a robust response against cancers. This innovative approach, however, still needs to address concerns, particularly surrounding gene editing’s safety and the potential immunorejection by recipient cells. 


The Future is “Off-the-Shelf”: 

With the strides in iPSC technology, the authors believe we’re on the brink of “off-the-shelf” therapies, ready for rapid global distribution. The prospect of banking third-party T-iPSCs or generating hypoimmunogenic iPSCs via HLA editing opens doors for an endless source of therapeutic T cells, all at a more affordable cost. This technology’s integration could lead to a brighter clinical prognosis and bring forth a new era in allogeneic cancer immunotherapy. 


In conclusion, this paper brilliantly traces the trajectory of allogeneic cell therapy, tackling its challenges head-on, and offering insights into the future of cancer treatment. 




Furukawa, Yoshiki, Yasuharu Hamano, Shuichi Shirane, Shintaro Kinoshita, Yoko Azusawa, Jun Ando, Hiromitsu Nakauchi, and Miki Ando. 2022. “Advances in Allogeneic Cancer Cell Therapy and Future Perspectives on “Off-the-Shelf” T Cell Therapy Using iPSC Technology and Gene Editing” Cells 11, no. 2: 269.