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Cyclophosphamide

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Imiquimod

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Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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Interferons

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

TAPA-pulsed DC vaccine

Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Cyclophosphamide Pill

Topical Imiquimod Cream will be applied after vaccination.

Imiquimod Topical Cream

Anthony Tolcher, MD

Patients diagnosed with progressive and/or refractory solid malignancies, who have failed conventional therapy, and have no available, potentially curative therapeutic options, will be candidates for this Phase I/II study. Following confirmation of disease progression and/or refractoriness, eligible patients who agree to participate and sign an informed consent form will have their tumor cells/tissues and/or blood analyzed for the expression of a specific panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.

For patients whose tumors express one (1) or more of these TAPAs (Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1), whole blood will be obtained by phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing GMP facility, according to established Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s) relevant for each particular patient. Patients will receive five (5) days of low-dose cyclophosphamide 5 to 7 days prior to each vaccination with TAPA-pulsed DCs to decrease Treg activity. Patients will also receive a single dose of topical Imiquimod cream after each vaccination. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs. DC vaccination schedule will be weekly via intradermal (ID) injections for a total of 3 vaccinations. Topical Imiquimod cream will also be administered once after the vaccination. Patients will be followed on a weekly basis (or more frequently if required) to evaluate treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per protocol specifications. Continuation and stopping rules for the study will be defined based on toxicity/tolerability (Phase I) and immune efficacy (Phase II).

Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies

Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Imiquimod, in Patients With Progressive and/or Refractory Solid Malignancies

Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.

The response of T-cells present in the peripheral blood mononuclear cells (PBMCs) population to the peptides used to pulse a patient's dendritic cell vaccine is evaluated by measuring the expression of Th1/CTL-type cytokines (IFN-γ and/or TNF-α and/or IL-17) by a standard ELI-Spot assay using 500,000 PBMCs per experimental replicate and a minimum of 3 experimental replicates for each stimulation. The results are expressed as the average number of spots obtained from the stimulation of 500,000 PBMCs

DTH skin test will be performed on subject's forearm or within 5 cm from the site of prior DC vaccination, if possible

Kiromic BioPharma Inc.

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

TAPA-pulsed DC vaccine: Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

Cyclophosphamide Pill: Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Imiquimod Topical Cream: Topical Imiquimod Cream will be applied after vaccination.

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