5 Abstracts Offer Snapshot of Immunology Research

The carcinoembryonic antigen (CEA) vaccinia has been researched for more than 20 years.

Investigational Glioma Vaccine Results Promising

A novel vaccine based on dendritic cells and peptides proved to be safe and capable of delivering an immune response in a phase I/II study in adults with recurrent malignant gliomas, with 2 patients sustaining a complete response and 9 patients experiencing progression-free survival (PFS) ≥12 months.

The results are so promising that phase II/III clinical trials are planned in recurrent glioblastoma (GBM), said lead author Hideho Okada, MD, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, who invented one of the peptides used in the vaccine.

The vaccine, now known as SL-701, consists of α-type-1 polarized dendritic cells loaded with synthetic peptides for gliomaassociated antigen epitopes. It was given in combination with the immunostimulant poly-ICLC. Patients were injected every 2 weeks for 4 injections with the possibility of boosters.

In all, 22 patients with grade 3/4 gliomas who tested positive for the human leukocyte antigen-A2 (HLA) participated in the study. The group included 13 patients with GBM, 5 with anaplastic astrocytoma, 3 with anaplastic oligodendroglioma, and 1 with anaplastic oligoastrocytoma.

There were no toxicities ≥grade 3, and injection-site reactions, transient fatigues, and chills were the most frequently reported adverse events. Okada said 13 of 16 patients experienced positive immune responses. In recurrent GBM patients, the median overall survival was 12 months. Abstract 2506

Survivin-derived Cocktail Provokes Immune Response

A peptide cocktail based partly on the promising antigen survivin stimulated de novo T-cell responses in many of the 53 patients with a variety of metastatic or locally advanced solid tumors vaccinated in a first-in-human trial from the University Hospital of Erlangen in Germany.

The open-label phase I study compared the immunologic efficacy, safety, tolerability, and clinical activity of 3 dosages of EMD640744 (30, 100, or 300 μg), which consisted of survivin-derived partially modified HLA class I-restricted peptides in a Montanide ISA 51 VG emulsion. Patients had to test positive for at least 1 relevant HLA antigen to participate.

Routine monitoring indicated T- cell responses in 14 of 38 patients (37%) assessed by IFNγ- ELISpot and in 31 of 42 patients (74%) assessed by HLA-multimer staining, including 16 responses (38%) that were clearly induced de novo. The most frequent tumor types were colorectal, ovarian, and melanoma.

Researchers suggested that the “remarkable number of successfully induced immune responses” may stem from the vaccine’s apparent ability to promote CD4-specifi c T cells. Abstract 2515

PSA-TRICOM Formulation Looks Safe and Effective

One serious fever and 3 minor ones were the main adverse reactions in a National Cancer Institute safety study of PSA-TRICOM, a vaccine composed of recombinant poxviruses with transgenes for the prostatespecific antigen (PSA) and 3 T-cell costimulatory molecules.

The randomized, vectorcontrolled phase II study also found that overall median survival improved 8.5 months among the 21 participants, who all had metastatic castrate-resistant prostate cancer.

Patients in 5 cohorts were placed on various intraprostatic vaccination and booster regimens. Tumor infiltrate was evaluated when adequate tissue was available.

Overall, a transient fever in 1 patient was the only grade 3 toxicity, and the most common grade 2 adverse events were fever (14.5%) and injection-site reactions (21%). Additionally, 16 of 21 patients had stable or improved PSA doubling time, 4 of 8 evaluable patients had immune response, and 11 of 15 patients had decreased or stable T regulatory function. A paired t-test of 13 biopsies pre- and postvaccination showed increases in tumor immunologic infiltrates.

Researchers concluded that intraprostatic administration of PSA-TRICOM is safe and can generate “a substantial immune response,” and that trials with clinical endpoints should be conducted. Abstract 2530

Dendritic Vaccine Plus Sunitinib Boosts Results in RCC

The combination of AGS-003, an investigational immunotherapeutic agent, and the tyrosine kinase inhibitor sunitinib demonstrated better results than would be expected from sunitinib alone in patients with newly diagnosed, advanced renal cell carcinoma (RCC).

AGS-003, created from autologous tumor RNA cells and dendritic cells, stimulates the proliferation of CD28-expressing cytotoxic T lymphocytes (CTLs) while sunitinib helps decrease regulatory T cells, suggesting synergistic effects, according to lead author Robert A. Figlin, MD, of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles, California.

The median progressionfree overall survival for the 21 participants was 11.9 months overall, including 14.9 months for intermediate-risk patients and 6.0 months for poor-risk patients. Six of 6 patients monitored for regulatory T cells showed a decrease following treatment, and 11 of 15 patients experienced increases in CTLs.

Plans are underway for a randomized, phase III trial comparing AGS-003 plus sunitinib versus sunitinib alone. Abstract 2532

Dendritic Vaccine Trumps Vector in Colorectal Study

A dendritic cell-based vaccine stimulated more T-cell responses against carcinoembryonic antigens (CEAs) than a poxvector formulation in a phase II trial involving patients with colorectal cancer who had undergone surgery and chemotherapy.

In all, 74 patients with no evidence of disease posttreatment were randomized 1:1 to receive either dendritic cells mixed with PANVAC-VF (poxvectors encoding CEA, MUC1, CD54, CD58, CD80) or PANVAC-VF along with local injections of granulocytemacrophage colony-stimulating factor (GM-CSF).

The dendritic cell vaccine resulted in significantly more T-cell responses against CEA than the poxvector (69% vs 41%), and also demonstrated a trend toward improved relapse-free survival (log rank P = 0.10).

The role of additional cytokines and regulatory cells and molecules in enhancing the adaptive immune response to the dendritic cell vaccine is being evaluated in ongoing studies, according to the research team led by Duke University Medical Center in Durham, North Carolina. Abstract 2533

For complete abstracts, visit ASCO Abstracts