First-in-human Interleukin-15-transpresenting Wilms' Tumor Protein 1-targeting Autologous Dendritic Cell Vaccination in Cancer Patients

Inclusion Criteria:

• Signed informed consent (i.e. date of study entry (T0))

• Age ≥ 18 years at the time of signing informed consent

• Diagnosis with a histologically or cytologically confirmed solid tumor of thepancreas, esophagus, liver or ovaries that is advanced, recurrent or progressingafter at least first-line anti-cancer treatment, or for which no alternativestandard therapy is available due to intolerance to or refusal of standard-of-caretreatment.

• Adequate hematological blood values following previous anti-cancer treatments, asjudged by the Principal Investigator

• All treatment-related toxicities must have resolved to CTCAE grade ≤ 2 or must bestable and well controlled with minimal, local or non-invasive intervention, asjudged by the Principal Investigator

• Reasonable life expectancy of at least 3 months, as estimated by the PrincipalInvestigator

• At least 1 measurable or evaluable lesion as defined by the latest version ofImmune-related Response Evaluation Criteria in Solid Tumors (iRECIST) guidelines

• Adequate hematologic and end-organ function, defined by the following laboratorytest results, obtained at the time of screening:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/µL) without granulocytecolony-stimulating factor support

• Lymphocyte count ≥ 0.5 x 109/L (500/µL)

• Platelet count ≥ 100 x 109/L (100,000/µL) without transfusion

• Hemoglobin ≥ 90 g/L (9 g/dL) (Patients may be transfused to meet thiscriterion)

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkalinephosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the followingexceptions:

• Patients with documented liver metastases: AST and ALT ≤ 5 x ULN

• Patients with documented liver or bone metastases: ALP ≤ 5 x ULN

• Total bilirubin ≤ 2 x ULN with the following exception:

• Patients with known Gilbert disease: total bilirubin ≤ 3 x ULN

• Creatinine ≤ 1.5 x ULN

• Albumin ≥ 25 g/L (2.5 g/dL)

• Phosphorus ≥ 0.78 mmol/L

• World Health Organization (WHO) performance status 0-2

• Willing or able to comply with the protocol, as judged by the Principal Investigator

• Women of child bearing potential must have a negative serum or urine pregnancy testat the time of screening. Women of child bearing potential and men must agree to useeffective contraception before, during and for at least hundred days after the laststudy treatment administration.

Exclusion Criteria:

• Use of any investigational agent within 4 weeks before the planned day ofleukapheresis

• Corticosteroid treatment within 1 week before leukapheresis, unless the PrincipalInvestigator rationalizes otherwise

• Active or history of autoimmune disease or immune deficiency, including, but notlimited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipidantibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barrésyndrome, or multiple sclerosis, with the following exceptions:

• Patients with a history of autoimmune-related hypothyroidism who are on thyroidreplacement hormone are eligible for the study.

• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimenare eligible for the study.

• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo withdermatologic manifestations only (e.g., patients with psoriatic arthritis areexcluded) are eligible for the study provided all of following conditions aremet:

• Rash must cover < 10% of body surface area

• Disease is well controlled at baseline and requires only low-potencytopical corticosteroids

• No occurrence of acute exacerbations of the underlying condition requiringpsoralen plus ultraviolet A radiation, methotrexate, retinoids, biologicagents, oral calcineurin inhibitors, or high potency or oralcorticosteroids within the previous 12 months

• Non-treated brain or meningeal mestases, or priorly treated brain or meningealmetastases with magnetic resonance imaging (MRI) evidence of progression in the last 8 weeks

• Pregnant or breastfeeding. Female subjects who are breastfeeding should discontinuenursing prior to the first dose of study treatment and until at least hundred daysafter the last study treatment administration

• Any other condition, either physical or psychological, or reasonable suspicionthereof on clinical or special investigation, which contraindicates the use of thevaccine, or may negatively affect patient compliance, or may place the patient athigher risk of potential treatment complications.