APN301 is a fusion protein of a humanized antibody (hu14.18) and IL2. The antibody portion specifically binds to the GD2 antigen that is expressed on tumors of neuro-ectodermal origin (such as sarcomas, neuroblastoma, melanoma, SCLC). IL2 is a cytokine that recruits multiple immune effector cell types. In patients, APN301 is designed to localize GD2-positive tumor cells via the antibody component. The fused IL2 then stimulates the patient’s immune system against the tumor by activation of both, NK and T cells, whereas the Fc portion of the antibody is designed to trigger tumor cell killing by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (see figure).

The immunocytokine was tested in several Phase I/II clinical studies in neuroblastoma and melanoma by i.v. delivery and has shown certain clinical activity.

Due to the recent success with APN311 (marketing authorization in the EU for the treatment of neuroblastoma) the development focus for APN301 has changed. Intratumoral injection of APN301 leading to an “in situ vaccination” effect has shown strong antitumor effects in several mechanistic mouse melanoma studies, in particular with low dose radiation and checkpoint blockade:

It is planned to investigate APN301 now in two clinical trials in melanoma as well as in GD2+ pediatric cancers (other than neuroblastoma) by low dose intratumoral injection aiming at induction of an immune response that may lead to systemic immunity. Both studies are in advanced preparation and will be commenced in Q3/Q4 2018.


Shusterman et al. Antitumor Activity of Hu14.18-IL2 in Patients With Relapsed/Refractory Neuroblastoma: A Children’s Oncology Group (COG) Phase II Study. J Clin Oncol. 2010 Nov 20;28(33):4969-75

Morris et al. In Situ Tumor Vaccination by Combining Local Radiation and Tumor-Specific Antibody or Immunocytokine Treatments. Cancer Res. 2016 76(13):3929-41

Morris et al. Tumor-specific inhibition of in situ vaccination by distant untreated tumor sites. Cancer Immunol Res. 2018 May 10 [Epub ahead of print]