ONCOLOGY

Visible Success with delNS-Based Immunotherapy Improved Equine Sarcoids

Scientists from the Viennese biotech company BlueSky Immunotherapies have used their experimental viral vector platform, delNS, to treat sarcoids in horses.

The oncology team of the University of Veterinary Medicine Vienna—led by Sabine Brandt and the sarcoid expert Edmund Hainisch—have achieved success that may lead the way toward the development of innovative and easy-on-the-body cancer therapies in humans, the company said.

Equine sarcoids are locally aggressive skin tumors, induced by the tumor antigens E6 and E7 of the bovine papillomavirus, which seriously compromise the health and welfare of the affected animals. Conventional treatment options such as surgical excision or chemotherapy have only limited effect and the tumors typically recur.

The equine sarcoids treated with delNS/E6E7 were completely and permanently eliminated, according to the paper. Moreover, the systemic delNS-mediated immune stimulation also eliminated non-injected sarcoids.

Intratumoral injection with iNSA/E6E7equ and/or iNSB/E6E7equ led to tumor regression even in equine patients with severe disease. A mare(ANC) with multiple, severe sarcoids affecting the right axilla, abdomenand inner thigh responded to intratumoral therapy. Injection of asingle lesion with iNSA/E6E7equ on days 0, 2 and 4, and iNSB/E6E7equ ondays 7, 9 and 11 by (white arrow indicates injection site) led tocomplete regression of the injected and all non-injected sarcoids within13 months as exemplarily shown for the right axilla. d0: day 0; m4:month 4; m10: month 10; m13: month 13.

Intratumoral injection with iNSA/E6E7equ on d0, d28, d86 led to tumor regression and no BPV1 DNA was detectable anymore from the tumor site. Amare (BEG) suffering from periocular mixed sarcoids (fibroblastic,nodular and verrucous components) shows complete tumor regression 10months after intratumoral injections (white arrow indicates injectionsite) with iNSA/E6E7equ on days 0, 28 and 86. Importantly, BPV1 E5 PCRfrom DNA of crusts collected from scarified skin (month 10) scorednegative (see inserted gel photo; BEG: patient DNA; L: GeneRuler DNALadder mix [ThermoScientific]; +c: sarcoid DNA as positive control: -c:equine intact skin DNA as negative control; ntc: sterile water asno-template control); d0: day 0; m5: month 5; m7: month 7; m10: month10.

The researchers also demonstrated that the papillomavirus that caused the sarcoids was eliminated.

With its proprietary delNS technology, the biotech company BlueSky Immunotherapies GmbH (Ltd.) has created a viral vector platform for the induction of interferon and the expression of tumor antigens. delNS-based vectors have many properties for overcoming the immunosuppressive environment of tumors, including:

• inducing a strong interferon response;

• activating T cells, dendritic cells and natural killer cells; and

• inhibiting immunosuppressive cells.

They designed, manufactured and used 2 types of delNS vectors for the local treatment (direct injection into the tumors) of the horses. Over 3 years, 29 horses received different treatment regimes.

Visible and very significant regression of the sarcoids was achieved in 20 of the treated horses, and 100% regression of the sarcoids occurred in 10 equine patients. Three horses had transient regression and 6 horses had no regression.

For more information:

Jindra C, Hainisch EK, Rümmele A, et al. Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients. PLoS ONE. 2021;16(11):e0260155. https://doi.org/10.1371/journal.pone.0260155