G. M. Mavligit

Chemoimmunotherapy of metastatic large bowel cancer. Nonspecific stimulation with BCG and levamisole

The administration of two chemoimmunotherapy programs to 103 consecutive patients with metastatic colorectal cancer resulted in improved survival for patients who achieved either objective tumor regressions or disease stabilization for more than 8 weeks. Objective tumor regression was observed in 47% of patients treated with the Ftorafur‐methyl‐CCNU‐methotrexate‐Bacillus Calm‐ette‐Guerin (FTOR‐MeM‐BCG) program and in 34% of patients treated with the 5‐fluorouracil‐methotrexate‐Bakers antifol (FU‐M‐BAF) ± Levamisole program. The combined median duration of survival for patients who achieved objective tumor regression and disease stabilization with FTOR‐MeM‐BCG was 13 months compared with 6 months for patients who had progression of disease (p = 0.001). The corresponding values for patients treated with FU‐M‐BAF ± levamisole were 11 months and seven months, respectively (p = 0.001). While the role of BCG immunotherapy in these results remains speculative, the administration of levamisole immunotherapy did not appear to have influenced results significantly. Patients who presented at diagnosis with Dukes A, B and C lesions, and therefore had longer disease‐free intervals, responded more frequently to chemoimmunotherapy and survived longer than patients who presented at diagnosis with Dukes D lesions. Similarly, greater antitumor effect was observed in patients with lower pretreatment plasma CEA levels. Evaluation of these pretreatment characteristics may have significant implications for the design of future clinical trials.

Immunotherapy of Human Cancer

The efficacy of the conventional modalities of cancer treatment—surgery, radiotherapy, and chemotherapy—has been reasonably well defined. There is also sufficient experience to permit one to predict the nature of future improvements in efficacy for these conventional modalities. For surgery, it is likely that the limit of efficacy has been reached, and while surgery can effectively cure a proportion of patients with apparent local disease, it is clear that disseminated, microscopic tumor deposits are present in at least half the operable cases at the time of surgery, ultimately eventuating in metastatic disease. A limited but important additional role for surgery will be the debulking of metastatic disease in an attempt to reduce the tumor burden and thus to improve the efficacy of subsequent systemic treatment with chemotherapy, immunotherapy, and other possible approaches.

Interaction between repeated skin testing with recall antigens and temporal fluctuations of in vitro lymphocyte blastogenesis in cancer patients

Abstract The effect of skin testing with recall antigens on lymphocyte blastogenesis in vitro was studied in 50 patients with carcinoma. Significant enhancement of lymphocyte blastogenesis to different mitogens was observed following the application of a skin test battery of recall antigens. No additional increments in blastogenesis were observed subsequently with repeated skin testing using a single recall antigen (dermatophytin). These results emphasized the possibility of a combined effect resulting from multiple factors on studies of lymphocyte blastogenesis.

ANTIGEN EXPRESSION AND CELL SURFACE PROPERTIES OF HUMAN LEUKEMIC BLASTS

It is well accepted that most human tumor cells express antigens that can evoke a cell-associated and/or humoral immune response. Antitumor antibodies reacting with human tumor antigens have been demonstrated in the sera of cancer patients by a variety of in vitro techniques. A major factor in understanding the host-tumor relationship has been the recent demonstration that many tumor cells also appear to be coated in vivo with immunoglobulin, particularly IgG. Indeed, most human and animal tumor cells tested thus far have been found to be coated in vivo with immunoglobulin.R* 13* 45-64* 56-57 , in Although the immunoglobulins have been eluted from human and animal tumors 1.89 IS. by many investigators, the intactness and immunological reactivity of these immunoglobulins have not been clearly established. The immunoglobulin coat may consist of specific antitumor antibodies bound to their target antigens, o r may be 61-61. 69 or both. The biological role of bound immunoglobulin is unclear. Most of the data supported the concept that bound immunoglobulins may decrease immunogenicity or antigenicity of the coated cell. Indeed, allo-antibodies to tumors can block lymphocyte-mediated cytotoxicity in vitro6-7. l2 and acid-eluted IgG can enhance tumor growth in

Modulation of the Immune Response of Guinea Pigs by Repeated BCG Scarification

Summary Immune competence to sheep erythrocytes, skin allografts, and antigenic tumor transplants was studied in random-bred CFDH as well as inbred (syngeneic) strain-2 guinea pigs receiving repeated BCG scarification. Peripheral blood leucocyte (PBL) changes and histopathological alterations of the skin site and regional lymph nodes were also evaluated during the course of treatment. The results demonstrate that in this experimental model BCG scarification depresses humoral immune competence and augments cellular immunity. Elevation of the PBL counts was also indicative of an acute systemic effect resulting from repeated BCG treatment. Flaring of previous scarification sites, activation and enlargement of draining nodes, and progressive responsiveness of nodes draining sites of previous scarification were also observed.

Histiocytic lymphoma in the brain as the only manifestation of relapse following remission maintainance with BCG immunotherapy

This report describes an unusual case of lymphoma which, after 54 months of complete remission induced with chemotherapy and maintained with BCG immunotherapy, relapsed in the brain alone. It is possible that the immuno‐therapy led to this pattern of relapse: this is supported by several other studies. The difficulty in diagnosing brain lymphoma is emphasized.

Inhibition of human lymphoma cell-line colony formation by lymphocytes from patients with lymphoma and cancer hospital employees.

Inhibition of human lymphoma cell‐line colony formation (ICF) was induced by peripheral blood lymphocytes (PBL) from patients with lymphoma and apparently healthy cancer hospital personnel. PBL from patients with nonlymphoma neoplasms and from normal blood bank donors did not elicit ICF. ICF was most marked when PBL were cocultivated for 24 hours in a ratio of 1000:1 with target lymphoma cells that had been cultured for 24 hours before exposure. No significant ICF was observed when target cells consisted of human neurogenic sarcoma, melanoma, colon adenocarcinoma, or Chinese hamster cells. It is possible that ICF is elicited by PBL sensitized to a cross‐reacting antigen present on the membrane of cultured lymphoma cells. This antigen may be synthesized by a transmissible etiologic factor.

Current Status of Human Cancer Immunotherapy

ABSTRACT Human cancer immunotherapy has been investigated for approximately 10 years. During that time, numerous clinical trials have been done with arbitrarily selected doses of BCG, C. parvum, MER, tumor cell vaccines, and levamisole. Smaller numbers of clinical trials have been done with other modalities of immunotherapy which fall into the categories of active specific immunotherapy, active nonspecific immunotherapy, adoptive immunotherapy, etc. While conflicting results in many of these trials are evident, immunotherapy does seem to have some clinical activity in a variety of human neoplasms. The most effective forms of immunotherapy at present are local regional immunotherapy and possibly immunotherapy with the immunorestorative agent, levamisole. The development of interferon for clinical trials and the preliminary results indicating activity in breast cancer, lymphoma, and multiple myeloma has opened the broad area of biological response modifier therapy to clinical investigation. The prospects for biological response modifier therapy with better defined and characterized agents, the doses and schedules of administration of which have been scientifically selected, offer the hope that biological therapy of cancer will develop as the fourth major modality of cancer treatment.

Adjuvant Chemotherapy and Immunotherapy in Colorectal Cancer

Colorectal cancer appears to be an ever-growing epidemic with an all-time high incidence of approximately 100,000 new cases estimated in the United States during 1977. This disease, which seems to affect males and females equally, has been subjected to numerous surgical therapeutic approaches during the past two decades. Unfortunately, these exhaustive conventional approaches have failed to improve the overall prognosis (Donaldson and Welch, 1974).

Tumor-related blocking of anti-fetal immunity.

Abstract A modified spleen colony assay was employed to evaluate the effect of various tumor-related factors upon the in vivo effectiveness of anti-fetal immunity. Reduction of fetal liver (hemopoietic) colony formation by in vitro incubation of fetal liver cells with lymph node cells sensitized to syngeneic fetal liver or plasma cell tumor was blocked by (1) solubilized fetal antigen, (2) serum from mice recently immunized with syngeneic fetal liver and (3) serum from patients with metastatic colon cancer. In the latter, the degree of blocking correlated with plasma CEA levels. Both humoral and cell-mediated mechanisms of anti-fetal immunity were blocked in plasma cell tumor-bearing mice, suggesting in vivo suppression of the immune response via circulating tumor-associated fetal antigen.