Immunotherapy Can Reject Intracranial Tumor Cells without Damaging the Brain despite Sharing the Target Antigen

Abstract

Although vaccines targeting tissue differentiation Ags represent a promising strategy for cancer immunotherapy, the risk of triggering autoimmune damage to normal tissues remains to be determined. Immunizing against a melanoma-associated Ag, dopachrome tautomerase (DCT), which normal melanocytes and glial cells also express, allowed concurrent analysis of autoimmune consequences in multiple tissues. We show that vaccination with recombinant adenovirus expressing DCT elicited a strong CTL response in C57BL/6 mice, leading to protection against intracranial challenge with B16-F10 melanoma cells. Both histological analysis and behavioral testing indicated that there was no evidence of neuropathology in vaccinated animals and long-term survivors. Although vitiligo or demyelination could be induced by additional stimuli (i.e., surgery or inflammation) in DCT-vaccinated mice, it did not extend beyond the inflammatory area, suggesting that there is self-regulatory negative feedback in normal tissues. These results demonstrate that it is possible to vaccinate against a tumor embedded in a vital organ that shares the target Ag.

Identity, Potency,In VivoViability, and Scaling Up Production of Lentiviral Vector-Induced Dendritic Cells for Melanoma Immunotherapy

“…2i). Since melanocytes present in the dermis and hair follicles express TRP2, this confirms autoimmune responses generated against TRP2, corroborating autoimmunity findings during melanoma immunotherapy trials in mouse studies and in humans (Shibagaki and Udey, 2003;Bridle et al, 2010). Other than these autoimmune effects, long-term survivors vaccinated with cryoSmartDC-TRP2 did not demonstrate signs of progressive autoimmunity or behavioral changes.…”

Transmigration of Melanoma Cells through the Blood-Brain Barrier: Role of Endothelial Tight Junctions and Melanoma-Released Serine Proteases

“…We have also used murine B16/F10 cells, which initially were adapted to form lung metastasis; however, they are able to form brain metastases as well [25], [26].…”

Heating it up: Oncolytic viruses make tumors ‘hot’ and suitable for checkpoint blockade immunotherapies

“…These considerations are even more important in the context of OVs and checkpoint inhibitor combinations, as OVs themselves are criticized for their potential to evoke autoimmune responses. 24 Thus, any potential OV-induced self-reactivities, 25 promoted during the priming phase of this combination therapy, could be exacerbated by the subsequent administration of checkpoint inhibitors, further augmenting the risk of adverse events.…”