Jules Harris

IMMUNOCHEMOTHERAPY OF LUNG CANCER

After surgical resection of their primary lung cancer, 33 patients were randomized into one of three groups. The first received high-dose methotrexate once per month with citrovorum rescue, for 3 months. The second group were immunized monthly with a homogenate of Freunds complete adjuvant and carefully characterized soluble antigen derived from allogeneic lung cancer cells of appropriate histology, for 3 months. The third group received a combination of methotrexate and immunization monthly, for 3 months. Each patient was monitored immunologically before, during, and after the treatment period, by use of delayed hypersensitivity reactions to recall and cancer antigens, in vitro lymphocyte response to mitogens, and mixed lymphocyte blocking factor activity. The group that received methotrexate showed little change in skin reactivity, a reduction of blocking factor activity, and significant rebound overshoot in in vitro lymphocyte performance. The immunized group showed a tendency to production of blocking factor activity, striking conversion and enhancement of skin reactivity, and little change in in vitro lymphocyte performance. The immunochemotherapy group showed dramatic increases in specific skin reactivity to cancer antigens, up to 2 years after treatment, in vitro lymphocyte rebound overshoot, and reduction of blocking factor activity production. Classic life table analysis of the probability of freedom from metastases in patients with stage-I cancer indicate that the disease-free interval in patients who received methotrexate is longer than in historic and concomitant controls but not as long as in those who received immunization. The best group appear to be those who received combination immunochemotherapy. We emphasize that the small numbers in this pilot study do not yet allow firm conclusions to be made.

In vitro Cellular Immunity and in vivo Delayed Hypersensitivity in Uremic Patients Maintained on Hemodialysis

Uremic patients on hemodialysis for periods in excess of 1 year have a significantly better survival rate for their renal allografts than do similar patients hemodialyzed for less than 1 year. Lymphoc

HLA Antigens in Bronchogenic Carcinoma

A decrease in the frequency of HLA-A2 was noticed in 37 bronchogenic carcinoma patients studied. HLA-B8 was found to be increased in the prolonged survivors of bronchogenic carcinoma.

Clinical Utility of Immunosuppressive Agents

Immunosuppressive drugs have two principal applications in clinical medicine. They are used in organ transplantation and autoimmune disease. The chemical suppression of the immune response has played an important part in human organ transplantation. Except where identical twins are involved, it is allogeneic grafts that are transplanted. Even with good tissue matching, there is some degree of histocompatibility difference between donor and recipient. In general, the less the histocompatibility difference the longer will be the survival of the grafted organ (van Rood, 1969; Festenstein et al., 1971; Sachs et al., 1971). Survival is further improved by the use of immunosuppressive drugs to abolish or impair the allograft rejection reaction of the recipient (Murray et al., 1963). The rationale for the use of drugs in a transplant situation is clear, and based on sound immunological considerations. In the case of autoimmune disease, however, the argument for the use of immunosuppressive drugs is less cogent. Many diseases are believed to be autoimmune in nature, that is, they are presumed to represent instances of humoral and cell-mediated immune reactivity within the body against antigenic determinants carried by normal tissue. Such an aberrant immune response against self is considered to be both initially responsible for the pathogenesis of the disease and for persisting tissue destruction during the later course of it.

Specific Active Immunotherapy in Lung Cancer: The Induction of Long-Lasting Cellular Responses to Tumour-Associated Antigens

In this report we give details of skin tests with soluble tumour-associated antigens in patients entered into the phase II trial of stage I lung cancer patients in Ottawa. We show that in non-immunized patients a weak positive reaction to such antigens following surgery is a favourable sign. Strong reactions in the group which received immunochemotherapy are associated with fewer failures than in the group which received immunization alone which had weak to moderate reactions. Strong delayed hypersensitivity reactions can be induced that endure more than 5 years. If such reactions indicate resistance to tumour growth, as in animal systems, then prophylactic immunization of healthy adults who are at high risk of developing lung cancer would be expected to reduce the incidence of the disease.

Specific Active Immunochemotherapy in Lung Cancer: A Survival Study

A radomized clinical trial of chemotherapy, immunization and immunochemotherapy among 55 patients with stages I and II carcinoma of the lung is reported. The survival rate in the immunized groups was significantly better (P = 0.001) than that in the nonimmunized groups. The results are discussed in the light of the reactivity of the patients to the specific cancer antigen.

Correlation in Hemodialysis Patients and Renal Allograft Recipients between Percent T Lymphocytes in Peripheral Blood and in vitro Lymphocyte Responses to Nonspecific Mitogenic Agents

Both hemodialysis and renal allograft recipients have a significantly reduced number of total T lymphocytes per microliter of blood. Simultaneous in vitro lymphocyte responsiveness to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) revealed in the normal subjects, a positive correlation (r = +0.427) between percent T lymphocytes and PHA and a negative correlation (r = -0.525) between percent T lymphocytes and PWM. Such trends were not observed in the hemodialysis patients and transplant recipients. Thus, the enumeration of lymphocytes as T cells appears to provide no clear indication of their functional capacity to respond to mitogenic stimulation in these two categories of patients.

Relationship of Blood Transfusions to Appearance of Mixed Leukocyte Culture Blocking Factor Activity in Plasma of Uraemic Patients and Renal Allograft Recipients

Abstract. Plasma samples from haemodialysis patients, renal allograft recipients and haemophiliacs were studied for the presence of mixed leukocyte culture blocking factor activity (BFA). A history of blood transfusions received within the preceding 6 months of testing was significantly and directly correlated with the appearance and persistence of BFA in the plasma of haemodialysis patients. This association was not found in renal allograft recipients. The development of BFA was found to be associated with formation of lymphocytotoxins but not haemagglutinins. The authors have also demonstrated that BFA resides in the IgG fractions of serum samples obtained from both chronic uraemics undergoing haemodialysis and patients bearing renal allografts. BFA may play a minor role in the acceptance of human renal allografts.

Lymphocyte Transformation in Human Plasma without Addition of Synthetic Medium

The in vitro response of lymphocytes obtained from normal subjects, uraemic patients on haemodialysis and diabetic patients was studied using cultures containing either medium plus plasma (medium cultures) or plasma alone (plasma cultures). The study demonstrated that plasma alone can adequately support lymphocyte transformation induced by nonspecific mitogens (PHA and PWM) and allogeneic lymphocytes in mixed lymphocyte culture (MLC) reaction. This investigation further confirms our previously reported findings that uraemic patients undergoing haemodialysis have a normal lymphocyte response in MLC and to PHA and PWM. Plasma cultures give results similar to conventional medium cultures in subjects where lymphocyte transformation is normal. The lymphocyte hyporactivity observed in diabetics is, however, better shown in the plasma cultures. The suppressed response of the diabetic patients lymphocytes to PHA and PWM both in the presence of autologous and normal AB plasma suggests intrinsic lymphocyte dysfunction as the explanation for impaired immune function. Plasma cultures may provide a better in vitro system for the evaluation of immune function in certain groups of patients where it is desirable to distinguish between intrinsic abnormalities of lymphocyte function and the effect of humoral immunosuppressive factors.

Beneficial Effect of Hemodialysis on Renal Allograft Survival

The effect of the length of hemodialysis on the outcome of renal transplant was evaluated in 43 recipients of renal allograft. 22 out of 23 patients (95.7%) dialyzed for longer than one year had an excellent renal function at one year, while only 10 out of 20 patients (50%) dialyzed for less than one year had good renal function at one year. Only one kidney (4.3%) was lost due to rejection in the first group, while 10 kidneys (50%) failed to function because of severe rejection in the second group. The length of hemodialysis appears to have a beneficial effect on graft survival, but the mechanism by which it exerts this effect is not clear.