An Engineered Nanoimmunotherapy for Melanoma

PROJECT SUMMARY
Melanoma is one of the most prevalent cancers and is estimated to account for overdeaths inin
the United States aloneAlthough highly curable when detected earlytheyear survival rates decline
precipitously for patients with regionaland metastaticmelanoma indicating a lack of efficacy
of conventional therapiesand a strong need for novel therapies for this patient populationIn response to this
needwe have engineered a nanoimmunotherapy for treating melanomawhich combines Prussian blue
nanoparticle based photothermal therapyPBNP PTTwith immune checkpoint inhibitionImmune checkpoint
inhibitors represent a class of monoclonal antibodies that target key immune checkpointswhich have resulted
in dramatic treatment responses in previously untreatable cancersparticularly metastatic melanomaDespite
this immense promiseresponses to immune checkpoint inhibitors are limited to small subsets of patients and
are associated with immune related adverse eventssome of which can be lethalThusthere is great need to
increase the efficacy of immune checkpoint inhibitors so that they elicit responses in a greater proportion of
treated patientsOur approach toward achieving this end is to engineer a nanoimmunotherapy which combines
PBNP PTT with anti PDand anti CTLAIn our nanoimmunotherapyPBNP PTT plus anti PDplus antiCTLAPBNP PTT serves the dual purpose of ablating the primary tumor to decrease tumor burden and
releasing tumor antigens to provide amulti antigen vaccination effectThese effects are complemented by
the administration of immune checkpoint inhibitorswhich decrease tumor immunosuppression and elicit a
potent antitumor immune responseWe anticipate that the interplay between the local immunomodulatory
effects of PBNP PTT with the reversing of immunosuppression elicited by the antibodies will result in complete
response and long term survival in a larger proportion of patients with melanomaThe goal of this project is to
test the feasibility of using this nanoimmunotherapy for treating melanoma in a syngeneic mouse model of the
diseaseIn Aimwe seek to demonstrate the efficacy of the nanoimmunotherapy in securing effective tumor
eradication and preventing relapseIn Aimwe seek to elucidate the immunological responses elicited by the
nanoimmunotherapySuccessful completion of this project will facilitate further preclinical development of our
nanoimmunotherapy in animal models of metastatic melanomaand ultimately clinical testing and
commercialization of our treatment regimen PROJECT NARRATIVE
The proposed research is relevant to public health because it could make available an effective and safe
treatment for melanomaa prevalent type of cancer that is expected to account for overdeaths inin the United StatesIt will also advance insights into the scientific merit and feasibility of combining
nanoparticle based photothermal therapy with immune checkpoint inhibition for treating melanoma in animal
modelsand the immunological basis for the observed treatment responsesSuccessful completion of this
project will facilitate future studies testing this combination nanoimmunotherapy in animal models of metastatic
melanomaan important prelude to clinical translation and commercialization of this treatment for patients with
melanoma