Not so long ago, immunotherapy against cancer was positioned as an emerging or even promising treatment, but not one with a proven track record. Todayowever, novel immunotherapeutics across different tumor types, either as monotherapy or in combination, are increasingly becoming one of the most innovative and powerful anti-cancer strategies.

One of the major challenges in ensuring that these novel treatments realize their true potential has been successfully equipping the immune system to launch its attack exclusively on tumor cells excluding all healthy tissues. Up until now.

Research led by Joaquín Arribas, Director of Preclinical Research at the Vall d'Hebron Institute of Oncology (VHIO), ICREA Professor, and Scientific Director of the Center for the Biomedical Research Network in Oncology (CIBERONC), has turned this obstacle into a therapeutic opportunity.

Published in Science Translational Medicine, the study, first co-authored by Irene Rius-Ruiz, Graduate Student of VHIO's Growth Factors Group, reveals that p95HER2-T cell bispecific antibody (TCB) can successfully guide immune cells, known as lymphocytes, directly to cancerous cells for their targeted killing.

p95HER2-TCB: guiding the immune system for the targeted killing of HER2-positive breast cancer cells

T cell bispecific antibodies constitute a promising approach in harnessing the immune system to mount its anti-cancer response and represent an increasingly valuable addition to the current arsenal against cancer. Not only are they highly specific but they can also hone in on one protein among tens of thousands, in this particular case, p95HER2.

Furthermore, each antibody molecule has a bipartite structure containing two protein-binding sites. This means that they can simultaneously attach to immune cells and cancerous ones as well as take the lymphocytes hand-in-hand directly to the malignant cells for their subsequent destruction.

Acting as a magnet that lures the patient's immune system solely to tumor cells, p95HER2-TCB enables a targeted response by attacking these cells directly without affecting normal cells.

"The immune system has the natural capacity to fight against disseminated disease. To do so more effectively, it must be better equipped to recognize and act against malignant cells," said Joaquín Arribas, corresponding author of the study.

He continues, "Thanks to the distinct specificity of p95HER2-TCB and p95HER2's exclusive location in tumor cells, we have achieved a 'home delivery' of immune-based therapy. Our findings represent an important step towards ensuring that the immune system can successfully deliver its powerful anti-cancer blows."

Immunotherapies for cancer are proving increasingly more effective in the treatment of metastatic disease. Generally, advanced and metastatic cancers eventually develop resistance to different lines of therapies. When patients eventually cease to respond to current therapies, leading to cancer cell spread, they have few therapeutic options available.