Herbert J. Rapp

Molecular basis of complement action

We may not be able to make you love reading, but molecular basis of complement action will lead you to love reading starting from now. Book is the window to open the new world. The world that you want is in the better stage and level. World will always guide you to even the prestige stage of the life. You know, this is some of how reading will give you the kindness. In this case, more books you read more knowledge you know, but it can mean also the bore is full.

Complement fixation on cell surfaces by 19S and 7S antibodies.

The mechanism of complement fixation on cell surfaces by whole antiserums, and by 19S and 7S fractions has been studied with a new comple-ment-fixation test. This test is based on the fixation and transfer of the activated first component of complement (Ć1a). We have concluded that a single molecule of 19S antibody in combination with antigen at the cell surface is sufficient to bind one molecule of Ć1a. For 7S antibodies at least two molecules in close proximity at the cell surface are required to fix one molecule of Ć1a.

CRITICAL REVIEW OF PREVIOUSLY REPORTED ANIMAL STUDIES OF TUMOR IMMUNOTHERAPY WITH NON‐SPECIFIC IMMUNOSTIMULANTS

A variety of immunostimulants can affect the growth of established syngeneic tumor transplants and autochthonous neoplasms. These immunostimulants include viable organisms, nonviable bacterial products, and chemically defined compounds (TABLE 1 ) . Viruses and bacterial endotoxins can also inhibit tumor growth, but it is not clear that they are primarily immunostimulants, and consideration of their complex mode of action is beyond the scope of this review. Over the last decade, there have been numerous attempts to cure established syngeneic or autochthonous tumors in guinea pigs, mice, rats, hamsters, cows, and primates by use of immunostimulants, alone or in combination with tumor cell vaccines. A substantial literature has accumulated, and progress has been made toward defining conditions for optimal immunotherapy. At present, however, our ability to control tumor growth with active immunotherapy is modest. With a few significant exceptions, systemic immunotherapy has failed to produce complete regression of palpable neoplasms. Local immunotherapy with Bacillus Calmette-Gukrin (BCG) and the corynebacteria can cure small tumor nodules and stimulate systemic tumor-specific immunity, but this approach depends on the introduction of an immunostimulant in close proximity to tumor cells, which is often difficult to achieve in clinical practice. Even when direct contact can be assured, some tumor lines have proven resistant to local immunotherapy. Given these limitations, it seems important to examine critically those systems where immunostimulants have been effective in order to identify factors that are likely to contribute to successful immunotherapy in human cancer.

Tumor Immunity Produced by the Intradermal Inoculation of Living Tumor Cells and Living Mycobacterium bovis (Strain BCG)

The intradermal inoculation of mixtures containing living tumor cells and living Mycobacterium bovis (strain BCG) into unimmunized syngeneic guinea pigs results in an inflammatory reaction to the BCG, and there is no progressive tumor growth. In the absence of BCG the tumor grows progressively, metastasizes, and kills the animal. By conventional methods, it has not been possible to immunize syngeneic guinea pigs to the tumor used. Guinea pigs that receive mixtures of BCG and tumor cells, however, develop specific systemic tumor immunity as measured by delayed cutaneous hypersensitivity and by suppression of tumor growth.

Immunotherapy of guinea pig cancer with bcg

An animal model for immunotherapy of cancer is described. Successful therapy required close contact between BCG and tumor cells, a host capable of developing and expressing delayed hypersensitivity type reactions to mycobacterial antigens, limited tumor size, and an adequate number of viable BCG. A nonliving mycobacterial preparation possessed potent tumor‐suppressive properties. This preparation, an oil in water emulsion, contained BCG cell walls attached to mineral droplets.

Neutralization of sensitized virus by the fourth component of complement.

Herpes simplex virus which had been sensitized with IgM antibody was not neutralized by the addition of the purified activated first component of complement. In the presence of an optimum concentration of the first component of complement, however, the sensitized virus was neutralized by the addition of a high concentration of the purified fourth component of complement. Under these conditions, the addition of the purified second and third components of complement failed to enhance virus neutralization. With low concentrations of the fourth component of complement, the addition of the second and third components enhanced virus neutralization.

Tumor hnmunity: Tumor Suppression in vivo Initiated by Soluble Products of Specifically Stimulated Lymphocytes

Supernatant fluids of specifically stimulated lymphocyte cultures were purified. Fractions containing migration inhibition factor when injected intra-dermally into strain-2 guinea pigs produced a reaction similar in appearance to delayed cutaneous hypersensitivity. There was an accumulation of mononuclear cells at the injection sites and the growth of syngeneic tumor grafts at the sites was suppressed.

Intralesional Immunotherapy of Melanoma with BCG

Treatment of recurrent cutaneous melanoma nodules with BCG is an effective and relatively nonmorbid method for eliminating these tumor nodules. Injected nodules can be made to disappear about 90 per cent of the time and in about 20 per cent of patients non-injected nodules in the same drainage area may also regress. Subcutaneous melanoma nodules are far more resistant to melanoma injection. Although cutaneous nodules can be made to regress there is no evidence that a systemic effect against disseminated melanoma exists and no responses of distant visceral disease have been seen following intralesional therapy of cutaneous nodules. The regression of cutaneous nodules following BCG injection appears to be an immunologic phenomenon and is related to the immunocompetence of the patient. The molecular mechanisms of this tumor regression are unknown and are the subject of intensive study. Several new approaches such as the use of BCG for the treatment of poor prognosis primary malignant melanomas, as well as the use of nonviable, nonbacteriologic agents for intralesional treatment are under investigation.

Immunologic approaches to the treatment of human cancer based on a guinea pig model

SummaryLocal immunotherapy is a form of cancer treatment where exogenous antigen is introduced into the area of the tumor. Under favorable circumstances, the perfused tumor regresses, systemic tumor-specific transplantation immunity is augmented, and distant microscopic metastases regress. Successful local immunotherapy requires an immunologically competent host, small tumor burden, and tumor located usually in the skin. A wide variety of biologic agents are capable of promoting local immunotherapy. BCG has been most widely studied. The antitumor activity of two different preparations of the Tice substrain of BCG were compared. No significant differences in antitumor activity were found. Alternative approaches to intralesional injection were sought. Intradermal injection of BCG adjacent to dermal tumors, prior to surgery, led to eradication of axillary metastases and to the development of tumor-specific transplantation immunity.Successful local BCG immunotherapy is a by-product of the host response to BCG infection. Involved are lymphocytes specifically sensitized to mycobacterial antigens, lymphocyte mediators, and macrophages which develop the capacity to kill tumor cells. Tumor-cell killing may be mediated by exocytosis of macrophage lysosomes into tumor cells. Complete and permanent tumor eradication probably requires the development of tumor-specific transplantation immunity mediated by sensitized lymphocytes. Local infection of the tumor may augment the development of this tumor-specific immunity.

Acquired cellular immunity: extracellular killing of Listeria monocytogenes by a product of immunologically activated macrophages.

Abstract A listericidal factor was released by monolayers of peritoneal cells from BCG-immune guinea pigs following incubation with PPD in cell culture. Significantly less listericidal factor was released by monolayers of BCG-immune cells incubated without PPD, or by monolayers of nonimmune cells incubated in the presence or absence of antigen. Culture supernatants containing listericidal factor were active at a dilution of 1:10, but supernatants diluted 1:100 were not listericidal. Dialysis of supernatants against fresh tissue culture medium did not affect their ability to kill Listeria, although heating at 60 °C for 30 min destroyed all activity. Supernatants from cultures of guinea pig fibroblasts or ascites-form hepatoma were not listericidal.