A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire
Fm. Batliwalla et al., A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire, MOL MED, 4(12), 1998, pp. 783-794
Citations number
55
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Background: The development of effective adjuvant therapies for the treatme
nt of high-risk melanoma patients is critical for the prevention of metasta
tic disease and improvement of patient survival. Active specific immunother
apy has been tested as an adjuvant treatment in numerous clinical trials wi
th overall limited, but occasionally promising, success rates. Newcastle di
sease virus (NDV) oncolysate has been utilized as an adjunctive immunothera
peutic agent in the postsurgical management of these patients. A phase II s
tudy initiated in 1975 using adjuvant vaccine therapy composed of allogenei
c and autologous human melanoma cells infected with live NDV (NDV oncolysat
e) in patients with AJCC stage III melanoma following therapeutic lymph nod
e dissection has shown >60% survival rate at 10 years with no adverse effec
ts. Continued long-term analysis of trials with promising early results as
well as assessment of immunologic responses generated in these patients may
result in improved therapeutic decisions for clinical trials in the future
.
Materials and Methods: We analyzed the 15-year survival of patients treated
postsurgically with NDV oncolysate in the phase II study described above.
In an attempt to understand the immunological effects of this treatment, we
have also carried out a comprehensive analysis of the peripheral blood T c
ell repertoire in these patients.
Results: The overall 15-year survival of this group of patients is 55%. Pre
vious studies have suggested that improved outcome in patients undergoing i
mmunotherapy is correlated with increased numbers of CD8(+)CD57(+) cells. I
n surviving patients, we observed a striking oligoclonality in the CD8(+) T
cell population in peripheral blood, which reflects clonal expansions in t
he CD8(+)CD57(+) subset.
Conclusions: The data suggest that adjuvant vaccination with NDV oncolysate
s is associated with prolonged survival of patients with lymph node-positiv
e malignant melanoma and that CD8(+) T cells may be an important component
of therapeutic efficacy.