Cancer vaccines: A two-pronged attack?

The latest findings in cancer vaccine development suggest that cancer vaccines may have two modes of action; specific immunization and non-specific activation of immune cells paralyzed by the tumor.

The human immune system fights cancer partly through the production of many populations of specialized immune cells called cytolytic T cells (CTL). Each CTL population recognizes a different, specific marker, an ’antigen’, on the cancer cell surface. Cancer vaccines are designed to tip the balance in favor of the immune system by stimulating the production of CTLs against the particular antigen in the vaccine. However, in back-to-back articles published today in the Journal of Experimental Medicine, investigators at the Brussels Branch of the Ludwig Institute for Cancer Research (LICR) and Brussel’s Louvain University have shown that a cancer vaccine not only specifically stimulates the production of CTLs against the vaccine antigen, it also non-specifically activates spontaneously produced CTL populations against multiple cancer antigens.

According to Dr. Thierry Boon, the Director of the LICR Brussels Branch, this observation opens a new way of thinking about how cancer vaccines might work. “We have always thought that cancer vaccines could only be effective if massive numbers of vaccine-specific CTLs were produced. But it seems that, in about 10% of patients with metastatic melanoma, the vaccine might actually be reawakening different CTL populations that have been effectively deactivated by the tumor.”

The research team also found that metastases were enriched with inactive CTLs, and they are now assessing exactly how vaccination can ’spark’ the reactivation of CTLs. “We believe that these CTLs in the metastatic lesions could potentially eliminate the bulk of the tumor,” says Dr. Boon. “Now we have to elucidate why this non-specific process works in some patients and not in others, and then to learn how to harness this effect to help even more people with cancer.”