## Solid Progress

When we previously discussed the progress of immunotherapy within cancer treatment, some of the most exciting results were in the field of leukaemia and melanoma, with progress in other solid cancers lagging somewhat behind. In the UK, solid tumour-forming cancers account for the overwhelming majority of cancer mortality for both females and males, so similar progress in these areas could have a transformative impact on the prognosis for sufferers.

The CAR-T approaches so successful with blood cancers are undergoing active trials in the UK and have already been approved as a treatment by the US FDA. Such techniques extract, modify and reintroduce the patient's immune cells after engineering the ability to target the cancer. This has the advantage of precision over standard cytotoxic chemotherapies, but the disadvantage of complexity (with the cost and time implications that follow from that), alongside the risks of initiating a dangerous systemic immune response.

Recent work examining the role of adjuvants to stimulate immune response in cancer vaccination show increasing promise. Researchers from Stanford recently trialled the combination of two immune-stimulating agents introduced directly into tumour sites within both single- and multiple-tumour mouse-models. The immune stimulating agents, CpG ODN and an anti-OX40 antibody, are already in use with human subjects. The degree of response in the lab animals was striking, not only impacting the tumour at the introduction site, but causing spontaneous remission of metastasised tumours throughout the body. Of 90 mice treated, 87 were completely cured of lymphoma in the first pass, with the remaining three suffering a recurrence cured by a second pass of the treatment. Successful results were also found in mouse models of breast cancer, so the treatment exhibits a degree of generality that will be doubtless be explored in subsequent human trials. Since this technique involves no personalised immuno-engineering, as a potential treatment it would be relatively inexpensive and straightforward. While the usual caveats about translating animal results to humans apply, both agents are in use individually within currently ongoing trials, which may permit accelerated introduction of the second agent in certain cases to assess efficacy within humans for various cancer types.

Pancreatic cancers are infamously difficult to treat, with survival rates stubbornly low over the last four decades. One reason for this is that the disease remains hidden until a late stage. Nearly half of sufferers are diagnosed only after presenting for emergency treatment, by which time the disease is usually deeply established and resistant to therapy. However, a novel therapeutic approach re-purposes a well-known enemy of our immune system. Research teams led from London's QMU engineered adenovirus-variants to not only target pancreatic cancer, but also deliver a newly developed non-toxic form of the immunotherapy agent Interleukin-12, thus harnessing nature's own nanotechnology to find, infect and eliminate tumour cells. With further trialling such viral engineering may provide a method of delivering effective treatment in cases that were previously beyond hope.

References

Nagle, S.J., Garfall, A.L., Stadtmauer, E.A. (2016) The Promise of Chimeric Antigen Receptor Engineered T cells in the Treatment of Hematologic Malignancies. The Cancer Journal: January/February 2016 - Volume 22 - Issue 1 - p 27–33 DOI: 10.1097/PPO.0000000000000166

Temizoz, B., Kuroda, E., Ishii, K.J. (2016) Vaccine adjuvants as potential cancer immunotherapeutics. International Immunology: Int Immunol. 2016 Jul; 28(7): 329–338. DOI: 10.1093/intimm/dxw015

Sagiv-Barfi, I., Czerwinski, D.K., Levy, S. et al. (2018) Eradication of spontaneous malignancy by local immunotherapy. Science Translational Medicine: Vol. 10, Issue 426, eaan4488; DOI: 10.1126/scitranslmed.aan4488

Man, Y.K.S. et al. (2018) The Novel Oncolytic Adenoviral Mutant Ad5-3Δ-A20T Retargeted to avβ6 Integrins Efficiently Eliminates Pancreatic Cancer Cells. Molecular Cancer Therapeutics: DOI: 10.1158/1535-7163.MCT-17-0671

Wang, Y. et al. (2018) Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent. Nature Communications: volume 8, Article number: 1395 (2017); DOI: 10.1038/s41467-017-01385-8

Assume we have a random variable, $$X$$, with expected value ... Read more