Although peptide-based cancer vaccines showed great promise, they have proved disappointing when it comes to treating tumours in clinical trials. The main reason for their failure? Their inability to efficiently deliver antigen peptides and adjuvants to lymphoid tissues, which means that only weak immune responses are seen.

Now, a team led by James Moon and Anna Schwendehman has developed an alternative strategy in which pre-formed non-toxic nanocarriers are mixed with adjuvants and antigen peptides, including tumour-specific mutant neo-epitopes, to produce personalized cancer vaccines. The researchers have designed high-density lipoprotein (HDL) nanodiscs made from simple phospholipids and apolipoprotein A1-mimetic peptides.

New nanodiscs do not trigger autoimmunity

“Thanks to their ultrasmall size (around 10 nm in diameter), the nanodiscs efficiently drain through lymphatic vessels after being injected into the body,” explains Schwendeman, “thereby significantly improving delivery of antigen peptides and adjuvants to lymphoid tissues.” And that is not all: compared with other HDLs (produced from purified human plasma, for example), the new HDLs do not trigger autoimmunity.

The nanodiscs can be used to deliver antigens to draining lymph nodes in the body and stimulate the activity of anti-tumour T-cells that significantly inhibit tumour growth. “They can also eradicate established tumours when combined with so-called immune checkpoint inhibitors (that work by removing the ‘brakes’ in immunosuppressed T-cells),” Moon tells nanotechweb.org. “And in experiments on mice, they even protect the animals from tumour recurrence.

EVOQ Therapeutics

“We have also shown that we can achieve potent personalized antitumor immune responses targeted to unique tumour mutations (or neo-antigens), which, in the majority of somatic mutations in cancer cells, are specific to each patient,” says Moon. “Coupled with recent innovations in tumour DNA/RNA sequencing, such a strategy may usher in a new era of personalized cancer immunotherapy if used with patient-specific antigens.”

The researchers, reporting their work in Nature Materials doi:10.1038/nmat4822, have created a new start-up EVOQ Therapeutics to translate their results to the clinic.