[mtwalsh01]

Antibodies and solid tumours

The previous article reports on some promising results obtained in animal studies with an antibody against CD47. The likely main efficacy of this antibody, should it pass the rigours of clinical trial testing, would seem to be for solid tumours. Various monoclonal antibodies have obtained regulatory approval to date as solid tumour therapeutic agents, all with different modes of action. These include trastuzumab, cetuximab, panitumumab, bevacizumab, catumaxomab, ipilimumab and denosumab. They target many different solid tumour types including, for example, breast, colorectal, head and neck, non-small cell lung cancers and melanomas.

As the previous article mentions, one of the challenges in developing a new cancer treatment is in targeting the drug to the tumour cells and in the case of a solid tumour, ensuring all the cancer cells are accessed. Thus much effort has been focused on development of effective drug delivery systems, which may be relevant as anti- CD47 enters clinical trials. One approach that has shown promise is the use of immunoliposomes. Studies are on-going to attempt modifications of liposomes that would allow efficient targeting of incorporated antibodies to their antigens. Nanoparticulate drug carriers are another potential method.

Another approach, which is different to the proposed use of anti-CD47 directly as a therapeutic agent, is to use the antibody to target the tumour and conjugate it to anti-tumour agents so that they can do their work. This has been examined, for example, in targeting alpha (v) integrins with antibody-maytansinoid conjugates containing anti-tumour maytansinoid-linker structures. Coupling of anti-GD2 antibody to liposomes has also been considered as a way to deliver siRNA in a targeted manner to neuroblastoma cells.

It is to be hoped that the promise of CD47 from animal studies will translate into successful clinical trials and drug development.

Sources

ADRIAN, J.E. et al., 2011. Targeted delivery to neuroblastoma of novel siRNA-anti-GD2-liposomes prepared by dual asymmetric centrifugation and sterol-based post-insertion method. Pharmaceutical research, 28(9), pp. 2261-2272

CHEN, Q. et al., 2007. Alphav integrin-targeted immunoconjugates regress established human tumors in xenograft models. Clinical Cancer Research: An Official Journal Of The American Association For Cancer Research, 13(12), pp. 3689-3695

DIENSTMANN, R., MARKMAN, B. and TABERNERO, J., 2012. Application of monoclonal antibodies as cancer therapy in solid tumors. Current Clinical Pharmacology, 7(2), pp. 137-145

HOLBACK, H. and YEO, Y., 2011. Intratumoral drug delivery with nanoparticulate carriers. Pharmaceutical research, 28(8), pp. 1819-1830

LEHTINEN, J. et al., 2012. Pre-targeting and direct immunotargeting of liposomal drug carriers to ovarian carcinoma. Plos One, 7(7), pp. e41410-e41410

PASTORINO, F. et al., 2013. Nanocarrier-mediated targeting of tumor and tumor vascular cells improves uptake and penetration of drugs into neuroblastoma. Frontiers In Oncology, 3, pp. 190-190

WILLINGHAM, S.B. et al., 2012. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proceedings of the National Academy of Sciences of the United States of America, 109(17), pp. 6662-6667