A new promise in cancer immunotherapy

The immune system is naturally programmed to target and attack tumours using T lymphocytes. As tumours grow, however, they can inhibit immune cells and escape immune detection, creating an internal reservoir of inhibited T cells.1 Immunotherapy, or the introduction of biological agents to boost immune function, has long been heralded as the holy grail of cancer treatment.2 Unfortunately, many current approaches incur high costs, involve long wait-times, and present the possibility of overdriving the immune system.3

Using mice models, researchers at Stanford University developed a combination therapy of two immune-stimulating agents to be injected into solid tumours.1 One agent, CpG, upregulates the expression of a receptor called OX40 on the surface of specific T cells. The other agent, an anti-OX40 antibody, stimulates the OX40 receptor and activates T cells within the tumour, allowing them to destroy cancerous cells.4 These T cells can then leave the original tumour and attack other identical, cancerous cells in distant, untreated metastases. Remarkably, the therapy resulted in complete elimination of cancer in 87 of the 90 mice subjects and regression after a second injection in the three remaining mice.1 This success can be balanced with safety, as the local administration of the treatment enables researchers to avoid overdriving the immune system and eliciting systemic side effects.

These results, despite their promise, must consider the significant differences between spontaneous tumours and transplanted tumours, which the initial experiments used.3 Although the researchers eventually mimicked spontaneous tumourigenesis with mice lacking an oncogene, effects in these animal models may not necessarily translate to humans. Nonetheless, the impressive preliminary success achieved with this combination therapy and the well-characterized nature of its two agents have encouraged its clearance for a clinical trial of 15 patients with low-grade lymphoma.1

Written by James Yu

References may be found in the journal

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