Table 3 Recombinant vaccinia virus (VV) vectors as cancer vaccines: representative clinical studies

TroVax

MVA

5 T4

A variety of agents (such as IL-2, IFN-α, sunitinib)

Phases II and III (n = 733)

Metastatic renal cancer

(1). Patients with good prognosis receiving vaccine + IL-2 had improved overall survival when compared to IL-2 alone. (2). Association between 5 T4-specific (but not MVA) antibody responses and enhanced survival.

[73, 195]

VV with A0201- restricted epitopes

MVA

Epitopes from gp100, MART-2 & tyrosinase

B7.1 and B7.2

(CD80 and CD86)

Phase I, II

Melanoma

Direct injection into lymph node, or given as a prime followed by peptide boosting; both gave antigen-specific CD8⁺ T cell responses. No overall survival benefit.

[64, 196]

TG4010

+ chemo

MVA

MUC1

IL-2

Phase 2b

Non-small cell lung cancer

TG4010 plus chemotherapy seems to improve progression-free survival relative to placebo plus chemotherapy. Because the primary endpoint was met, the trial will continue into phase III.

[82]

MVA-brachyury-TRICOM

MVA

Brachyury

TRICOM [B7.1, ICAM-1, LFA3]

Phase I (n = 38)

Advanced cancer patients

Brachyury-specific T-cell responses were observed at all dose levels and in most patients.

[197]

PROSTVAC

VV prime and fowlpox boost

PSA

TRICOM [B7.1, ICAM-1, LFA3]

Phase II

Prostate cancer

Increased PSA-specific CTL responses, particularly with GM-CSF or IL-2. In prostate cancer, an increase in progression-free survival was observed.

[78, 79]

PANVAC

+ chemo

(docetaxel)

PANVAC (VV and fowlpox)

CEA and MUC1

Just PANVAC or none (chemo alone)

Phase II (n = 48)

patients with metastatic breast cancer

Combination of PANVAC with docetaxel provides a clinical benefit. The median progression-free survival was 7.9 months in the combination group vs. 3.9 months in the chemo group.

[86]