Cancer: Improving cancer vaccine design

A new type of cancer vaccine that can thwart the defensive response of tumours to vaccine-induced immune attack, is presented in Nature. Preliminary results demonstrate the efficacy and safety of this vaccine in mice and nonhuman primates. The preclinical findings could pave the way for further testing to determine clinical applicability.

Most cancer vaccines target the specific cell surface proteins (antigens) that are expressed by tumour cells, helping the immune system to recognize and attack these cells. However, the nature and immunogenicity (ability to stimulate an immune response) of these antigens is unique to each individual, limiting the development of a universal vaccine. Furthermore, tumours can often escape immune attack by mutating and altering antigen presentation, thereby reducing their recognition.

Kai Wucherpfennig and colleagues present a new design of cancer vaccine that can overcome individual variations in tumour immunity by targeting two major types of immune cells (T cells and natural killer (NK) cells) and eliciting a coordinated, general attack independent of the tumour’s antigens. This vaccine targets two types of surface protein — MICA and MICB — whose expression is increased under stress in various human cancers. T cells and NK cells are normally activated by binding to these stress proteins, yet tumour cells can evade this attack by slicing MICA and MICB and shedding them. This vaccine, however, can prevent this slicing, thereby increasing the amount of stress protein expression and, consequently, facilitating the stimulation of an orchestrated, dual attack from T and NK cells. The authors reveal that this vaccine is both efficacious and safe in preliminary experiments using mouse and rhesus macaque models.

The authors conclude that these initial results reveal that this vaccine is capable of promoting protective immunity against tumours, even those with evasive mutations. Future clinical trials will be needed to evaluate this potential in humans.