Allogeneic retrovirally transduced, IL‐2‐ and IFN‐γ‐secreting cancer cell vaccine in patients with hormone refractory prostate cancer—a phase I clinical trial

Abstract

Immunisation with the allogeneic LNCaP/IL-2/IFN-gamma vaccine is safe and feasible without any dose-limiting toxicity or autoimmunity. A 50% PSA decline was achieved in two of the six patients. This encouraging data provides the scientific rationale for further investigation of the vaccine in a phase II trial.

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

“…Peptide synthesis was performed as described previously. 47 An irrelevant HLA-A2-restricted peptide from the CML fusion protein bcr3/abl2 (SSKALQRPV 926À934 ) 48 was used as a negative control and the HLA-A2 cytomegalo-, EBV-and influenza (flu)-virus peptide pool (CMV pp65 NLVPMVATV 495À503 , EBV-BMLF1 GLCTLVAML 280À288 , EBV-LMP-2 CLGGLLTMV 426À434 , influenza M1 protein GILGFVFTL 58À66 and influenza RNA polymerase PA FMYSDFHFI 46À54 ) with 0.2 mg of each peptide per well as a positive control (PANATecs GmbH, Tübingen, Germany).…”

Entering a New Era – Prostate Cancer Immuno-Therapy After the FDA Approval for Sipuleucel-T

“…The two cytokines chosen for this approach have been used for immunostimulation solely and in combination in a variety of tumors (Brill et al, 2007;Dieli et al, 2007) and both substances are FDA approved single agents. Expression of tumor-associated antigens is upregulated after treatment with IFN via IFNinducible genes, thereby increasing the susceptibility of tumors to MHC restricted CD8+CTL-mediated killing (Gansbacher et al, 1990a;Shankanan et al, 2001;Propper et al, 2003;Dunn et al, 2005).…”

“…LNCaP cells, as mentioned above (see GVAX) express some relevant TAAs but in contrast to other PCa cell lines used as cancer vaccines, do not express transforming growth factor (TGF)-. After detailed investigation of the safety profile with special attention to induction of autoimmunity (n = 3 patients at a dose level of 7,5 × 10 6 cells) (Brill et al, 2007), further patients (n = 27) were scheduled to receive four intradermal vaccine injections (dose level of 1.5 × 10 7 cells) on days 1, 15, 29, and 92. In the absence of disease progression, patients received further vaccinations every three months -resulting in a total amount of more or less 100 million cells/year -as compared to 4,600 million used in other trials (see GVAX).…”

“…OnyP (Michael et al, 2005) PSCA as target (Thomas-Kaskel et al, 2006) e.g. LNCaP/IL2/IFN (Brill et al, 2007(Brill et al, , 2009 Telomerase as target (Vonderheide et al, 2004;Su et al, 2005) 1.1.4 whole tumor cells (modified in situ -"in situ vaccination") 2.1.2 DCs pulsed ex vivo with multiple peptides Cell modification via viral vectors e.g. AdV-IL2 (Simons et al, 1999) DCs pulsed "peptide cocktail" diff.…”

Manipulation of MHC-I/TCR Interaction for Immune Therapy

“…An allogeneic prostate carcinoma cell line, LNCaP transduced with the IL-2 and IFN-γ genes, could express IL-2 and IFN-γ. In a phase I trial, the irradiated cells were transferred into HLA-A2-matched patients with hormone refractory prostate cancer (HRPC) (103). Two of the six patients produced effective anti-tumor response.…”