3.2 Progress in the investigation of vaccines for active-specific 
immunotherapy. 
The clinical trials of vaccines for active-specific immunotherapy have had some 
success with three types of malignancy; renal carcinoma, colon carcinoma, and 
malignant melanoma. The methodologic requirements for cancer vaccines have 
gradually been worked out in animal models in the last 15 years. Many clinical trials in 
this field were initiated before this information was available, or did not adhere to the 
methodologic requirements that had been found in the animal studies. As a 
consequence, there are several clinical investigations of active immunotherapy failed 
due to study design or preparation of the tumor vaccine. These studies may have 
failed due to one of the following factors; (A) The tumor cells should be preserved in a 
viable form in those vaccines where whole tumor cells are used. (B) Each procedure 
toward a subcellular product must be carefully evaluated as the immunogenicity can 
be easily destroyed. (C) The cryopreservation procedure for strong tumor cells for a 
later use in the vaccine must be carefully evaluated and shown not to destroy the 
immunogenicity of the vaccine. (D) The use of an adjuvant is essential, but the 
adjuvant must be given at a predetermined optimal concentration. Tumor cell 
vaccines are considered to be weakly antigenic and the use of an effective adjuvant is 
critical to success, but selection of the wrong dose can negate the adjuvant’s role. (E) 
The dose of tumor cells or quantity of antigenic material is a critical factor and when an 
inadequate dose is given, the immunologic effect will be lost. (F) The animal studies 
had predicted that the use of the patient’s own tumor cells (autologous) would have 
the highest likelihood of success, while allogenic cells were often unsatisfactory. 
However, the use of allogeneic cell lines would have great practical advantages of 
standardization, availability, and ease of vaccine preparation. 
Allogeneic approaches have begun to show promise in the treatment of malignant 
melanoma where some regressions of metastatic disease have been observed (5, 6) 
and preliminary but non-randomized studies for early melanoma have shown promise 
(7, 8). 
One of us (C.M.) has been conducting trials on the concept of active-specific 
immunotherapy for metastatic kidney carcinomas using autologous tumor cells and C. 
parvum as an adjuvant. The vaccine was administered weekly for six weeks, 3 of 14 
patients underwent objective regressions in the initial study (9), and 5 of 20 patients 
responded in a second trial (10). Several of the responding patients had remissions 
lasting from 2-5 years and some remain in remission. Skin testing was included by 
using autologous tumor cells for a portion of these renal carcinoma patients; the 
rationale was that if immunity to tumor cell membrane antigens is achieved, there 
should also be delayed cutaneous hypersensitivity on skin testing with those same 
tumor cells as had been observed in animal tumor models. Below are two figures 
summarizing our experiments with this group of renal carcinoma patients (11). In 
figure 1, the skin testing results shown for 18 patients who were tested prior to and 
following the treatment protocol. Eight of the eighteen patients became skin test 
positive patients, three had objective partial responses and the fourth had a minor 
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