RT Journal Article
SR Electronic
T1 Nasal administration of recombinant <em>Neospora caninum</em> secreting IL-15/IL-15Rα inhibits metastatic melanoma development in lung
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e006683
DO 10.1136/jitc-2023-006683
VO 11
IS 5
A1 Arthur Battistoni
A1 Louis Lantier
A1 Anne di Tommaso
A1 Céline Ducournau
A1 Laurie Lajoie
A1 Mahtab Samimi
A1 Loïs Coënon
A1 Clément Rivière
A1 Mathieu Epardaud
A1 Leslie Hertereau
A1 Agathe Poupée-Beaugé
A1 Juliette Rieu
A1 Marie-Noëlle Mévélec
A1 Gordon Scott Lee
A1 Nathalie Moiré
A1 Stephanie Germon
A1 Isabelle Dimier-Poisson
YR 2023
UL http://jitc.bmj.com/content/11/5/e006683.abstract
AB Background Metastases are the leading cause of mortality in many cancer types and lungs are one of the most common sites of metastasis alongside the liver, brain, and bones. In melanoma, 85% of late-stage patients harbor lung metastases. A local administration could enhance the targeting of metastases while limiting the systemic cytotoxicity. Therefore, intranasal administration of immunotherapeutic agents seems to be a promising approach to preferentially target lung metastases and decrease their burden on cancer mortality. From observations that certain microorganisms induce an acute infection of the tumor microenvironment leading to a local reactivating immune response, microbial-mediated immunotherapy is a next-generation field of investigation in which immunotherapies are engineered to overcome immune surveillance and escape from microenvironmental cancer defenses.Methods The goal of our study is to evaluate the potential of the intranasal administration of Neospora caninum in a syngeneic C57BL6 mouse model of B16F10 melanoma lung metastases. It also compares the antitumoral properties of a wild-type N. caninum versus N. caninum secreting human interleukin (IL)-15 fused to the sushi domain of the IL-15 receptor α chain, a potent activator of cellular immune responses.Results The treatment of murine lung metastases by intranasal administration of an N. caninum engineered to secrete human IL-15 impairs lung metastases from further progression with only 0,08% of lung surface harboring metastases versus 4,4% in wild-type N. caninum treated mice and 36% in untreated mice. The control of tumor development is associated with a strong increase in numbers, within the lung, of natural killer cells, CD8+ T cells and macrophages, up to twofold, fivefold and sixfold, respectively. Analysis of expression levels of CD86 and CD206 on macrophages surface revealed a polarization of these macrophages towards an antitumoral M1 phenotype.Conclusion Administration of IL-15/IL-15Rα-secreting N. caninum through intranasal administration, a non-invasive route, lend further support to N. caninum-demonstrated clear potential as an effective and safe immunotherapeutic approach for the treatment of metastatic solid cancers, whose existing therapeutic options are scarce. Combination of this armed protozoa with an intranasal route could reinforce the existing therapeutic arsenal against cancer and narrow the spectrum of incurable cancers.Data are available upon reasonable request.