Active specific immunotherapy for malignant melanoma with allogeneic melanoma vaccine dynamics of immunological parameters along with clinical response

1993 ◽  
Vol 6 (1) ◽  
pp. 12
Author(s):  
Hidekazu Tsukamoto ◽  
Kazuhito Hayashibe ◽  
Masamitsu Ichihashi
Author(s):  
Xinhui Wang ◽  
Smruti Desai ◽  
Elvyra J. Noronha ◽  
Abraham Mittelman ◽  
Soldano Ferrone

1994 ◽  
Vol 12 (2) ◽  
pp. 396-401 ◽  
Author(s):  
M S Mitchell ◽  
P E Liggett ◽  
R L Green ◽  
J Kan-Mitchell ◽  
A L Murphree ◽  
...  

PURPOSE To determine whether active specific immunotherapy with lysates of cutaneous melanoma cells, administered with immunologic adjuvant DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT), is effective in shrinking a primary choroidal melanoma, in an elderly patient already blind in the nontumorous eye. An 81-year-old man was referred with a primary choroidal melanoma of the left eye, with virtual blindness of the right eye due to macular degeneration. He was begun on active specific immunotherapy with an experimental melanoma vaccine (melanoma theraccine) and DETOX on weeks 1, 2, 3, 4, and 6, respected after a hiatus of 2 weeks. After a response was noted, monthly injections were given. RESULTS The patient had a significant shrinkage of his choroidal melanoma from a height of 4.2 mm to 2.4 mm within 2 months. This was sustained by continual treatment for 21 months until September 1991. After the patient failed to return for 9 months while recuperating from a stroke, the lesion regrew to a height of 3.7 mm and developed an additional lobe. On resumption of monthly treatments, the lesion shrank to 3.4 mm within 3 months, lost the additional lobe, and has since remained stable. No metastases have been found over a period of nearly 4 years on quarterly computed tomographic (CT) scanning of the chest and abdomen, and magnetic resonance imaging of the head. CONCLUSION Active specific immunotherapy with cutaneous melanoma lysates has caused a clinically useful protracted regression of a primary choroidal melanoma in an elderly patient in whom surgery and radiation therapy were contraindicated. This may represent the first case of a primary choroidal melanoma, and perhaps the only primary tumor, successfully treated with systemic immunotherapy alone. A formal trial of active specific immunotherapy for primary choroidal melanoma in selected patients may be warranted.


1994 ◽  
Vol 12 (2) ◽  
pp. 402-411 ◽  
Author(s):  
M S Mitchell ◽  
J Jakowatz ◽  
W Harel ◽  
G Dean ◽  
L Stevenson ◽  
...  

PURPOSE To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response. PATIENTS AND METHODS Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine. RESULTS Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone. CONCLUSION These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.


2008 ◽  
Vol 207 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Rachel Rosenthal ◽  
Carsten T. Viehl ◽  
Ulrich Guller ◽  
Walter P. Weber ◽  
Michel Adamina ◽  
...  

1989 ◽  
Vol 5 (6) ◽  
pp. 420-425 ◽  
Author(s):  
Donald L. Morton ◽  
Leland J. Foshag ◽  
J. Anne Nizze ◽  
Rishab K. Gupta ◽  
Estela Famatiga ◽  
...  

1992 ◽  
Vol 216 (4) ◽  
pp. 463-482 ◽  
Author(s):  
DONALD L. MORTON ◽  
LELAND J. FOSHAG ◽  
DAVE S.B. HOON ◽  
J. ANNE NIZZE ◽  
LESLIE A. WANEK ◽  
...  

1992 ◽  
Vol 10 (7) ◽  
pp. 1158-1164 ◽  
Author(s):  
M S Mitchell ◽  
W Harel ◽  
S Groshen

PURPOSE Only a proportion of patients with disseminated melanoma who were immunized successfully with a therapeutic melanoma vaccine (theraccine) had a major clinical response. We investigated whether there was a correlation between their HLA phenotypes and the likelihood of a clinical response. PATIENTS AND METHODS Seventy patients with disseminated melanoma who were treated with melanoma theraccine were HLA-typed serologically. The two melanoma cell lines used in the theraccine also were typed by serology and cDNA probes (for class II). Results were analyzed to see whether any alleles were present or absent in responders consistently. RESULTS The HLA class I alleles A2 (and the cross-reacting A28), B12 (and its split B44 and B45), and C3 were found to be associated with clinical remission. The effects of these alleles on response were apparent when two or more of the alleles were analyzed together. There was a 38% response rate in those 24 patients with two or three of the alleles compared with 20% in the group as a whole. CONCLUSIONS These data support two distinct possibilities between which we cannot yet distinguish. Responses may be more likely when there is a close match between the HLA molecules in the theraccine and the patients' own molecules. Alternatively, certain types of HLA class I molecules present in the patients may facilitate rejection of autochthonous melanomas by efficiently presenting melanoma-associated antigens to cytotoxic T cells.


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