Trial Information

Phase1/2 Study of Vaccination With DNP Modified Autologous Renal Cell Carcinoma in Combination With Sunitinib in Stage 4 RCC

Background: Renal cell carcinoma (RCC) constitutes around 3% of all solid tumors and cure
for metastatic sidease is reported for less than 5% of patients. Together with melanoma it
is considered the most immune responsive tumor, moreover it is a common practice to resect
primary tumor or large metastasis even in the metastatic settings. Antiangiogenesis
treatments are currently the favored antitumor drugs, however their use has rarely resulted
in complete response/ cure. Recently it has been demonstrated that these drugs can elicit a
shift in the immune environment in RCC patients (improved T1 responses reduced Treg
responses).Our department has experience in the treatment 200 melanoma patients with
cellular vaccination and in the preparation of primary tumor cell lines from various tumors
including RCC. Interestingly , immune modulators such as antiCTLA-4 Ab have demonstrated
impressive activity in patients previously vaccinated with cellular vaccinations.

Working hypothesis: Vaccination with autologous cellular vaccines of RCC patients will
induce clinical and immunological responses and help in formulation of better combined
vaccination strategies in this cancer. Our aims are: 1) Growth and characterization of
primary RCC cell lines,2)vaccination with autologous cellular vaccines in combination with
sunitinib. 3) Clinical and immunologic characterizations for derivation of prognostic and
predictive factors.

Methods: primary or metastatic tumor resected in one of several Israeli hospitals will be
used to derive autologous cell lines used for vaccinations following DNP modifications in
combination with the regular Sunitinib treatments. Immunological and clinical followup of
the patients will be performed and primary cell lines will be grown for further in-vitro
testing including possible future use for allogeneic vaccines. Expected result Good safety
profile combined with significant clinical and immunological responses are expected.

Importance: This research might result in clinical benefit to the treated patients and will
be important in the formulation of effective immune strategies in kidney cancer.

Probable implications to Medicine: RCC vaccine in combination with other therapies has the
potential to lead to longer survival and even cure the proposed study will help in the
formulation of such a vaccine.