Human Monoclonal IgM Research Articles

Lethal shock induced by administration of human IgM monoclonal antibody reactive to SWAP-70

Lethal shock induced by administration of human IgM monoclonal antibody reactive to SWAP-70

Anti‐Beta‐2 Glycoprotein I Antibodies Affect Bcl‐2 and Bax Trophoblast Expression without Evidence of Apoptosis

Antiphospholipid antibodies (aPLs) reacting with beta-2 glycoprotein I (beta2GPI) have been associated with recurrent fetal loss and pregnancy complications. The aim of the study was to investigate whether aPLs with anti-beta2GPI specificity induce apoptosis of human trophoblasts in vitro. To this end, human anti-beta2GPI monoclonal IgM derived from a patient with antiphospholipid syndrome and a human irrelevant monoclonal IgM were incubated with human trophoblast cell cultures for 24, 48, and 72 h. In all the cultures we evaluated: (i) Bcl-2 and Bax mRNA and protein expression by Western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively; (ii) DNA fragmentation by a commercial ELISA kit and by agarose gel electrophoresis; and (iii) the percentage of cells reactive with the monoclonal antibody (MAb) M30 by indirect immunofluorescence. The results were: Bcl-2/Bax ratio increased in untreated trophoblast cells during the time of culture, showing the highest values detectable after 72 h (2.68 and 2.28 at protein and mRNA levels, respectively). Cell incubation with anti-beta2GPI MAbs induced a significant Bcl-2/Bax ratio reduction in comparison with untreated cells (1.22 and 1.28 at protein and mRNA levels, respectively, after 72 h incubation). No significant difference was detected after cell exposure to irrelevant MAbs. However, neither DNA fragmentation nor increase in cells positive for the caspase-cleaved epitope of cytokeratin 18 cytoskeletal protein (M30) was found. In Conclusion, anti-beta2GPI antibodies react with trophoblast cells and reduce the Bcl-2/Bax ratio, but without any clear apoptotic effect.

Diagnostic Surface Expression of SWAP‐70 on HIV‐1 Infected T Cells

Following immunization with HIV-1 infected cells, a hybridoma cell line termed 9F11 was established from the P3U-1 myeloma line fused with lymphocytes from a trans-chromosome (TC) mouse, that harbors human chromosomes containing immunoglobulin genes. The 9F11 human IgM monoclonal antibody (9F11 Ab) reacts with HIV-1 infected MOLT4 cells but not with uninfected MOLT4 cells, and causes immune cytolysis with homologous human complement at a concentration as low as 0.4 microg/ml. This Ab was used to perform immunoscreening of a cDNA expression library derived from HIV-1 infected cells. All positive cDNA clones contained SWAP-70 cDNA. SWAP-70 RNA and protein expression are much stronger in HIV-1 infected cells. SWAP-70 was also detected on the surface of HIV-1 infected cells by flow cytometric analysis. The monocyte cell line U937 cells expresses SWAP-70 on its cell surface regardless of whether it was infected with HIV-1. Furthermore, among PBMCs surface expression of SWAP-70 was detected on CD21+, CD56+ and CD14+ cells. Although CD3+ cells scarcely express SWAP-70 on their surface, once activated, they become positive. SWAP-70 may therefore serve as a marker for T cell differentiation as well as for HIV-1 infection.

The natural human monoclonal IgM antibody LM-1 inhibits human lung cancer growth in vitro and in vivo

7347 Background: Lung cancer is a major cause of mortality worldwide and the overall survival rate has not improved significantly in the past 20 years. Of the more than 150,000 new cases of lung ca...

Human IgM Monoclonal Antibodies Reactive with HIV‐1‐Infected Cells Generated Using a Trans‐Chromosome Mouse

The trans-chromosome (TC) mouse that we used harbors human chromosomes 2, 14 and/or 22, and has undergone knock-out of its endogeneous genes coding for mu-and kappa-chains of immunoglobulin. One of these TC mice was immunized with HIV-1-infected U937 cells, and spleen cells from the immunized animal were fused with the mouse myeloma cell line to generate hybridoma cells. We selected hybridomas that produce human IgM antibodies (Abs) reactive with HIV-1-infected MOLT4 cells but not with uninfected MOLT4 cells. Two hybridoma cell lines were established termed 9F11 and 2G9. Although 0.4 mug/ml of 9F11 was able to induce complement-mediated cytolysis of the infected cells in the presence of fresh human serum, 2G9 could not. There was no difference between the two monoclonal Abs in the base sequences of cDNAs coding for the constant regions of mu-and kappa-chains. Therefore, we speculate that the ability to activate complement on homologous cell membranes might reflect the structural presentation of antigenic molecules, which could facilitate the binding of an IgM Ab to multiple binding sites resulting in escape from restriction by species-specific inhibitors of complement such as DAF (CD55) and CD59. On the other hand, 2G9 induced apoptosis of HIV-1-infected cells, including latently infected OM10.1 cells, although the Ag for 2G9 remains to be identified. Since both of the Abs had reduced reactivity toward HIV-1-infected MOLT4 cells following cultivation in the presence of tunicamycin, the responsible antigens would involve a sugar moiety.

Human antibody SC-1 reduces disseminated tumor cells in nude mice with human gastric cancer

Advanced gastric cancer is a systemic disease that requires adjuvant therapy targeted at eliminating disseminated tumor cells (DTCs). We investigated whether the apoptosis-inducing human monoclonal IgM antibody SC-1 was able to reduce the number of disseminated gastric cancer cells in blood and bone marrow. Human gastric tumor specimens with positive expression of the SC-1 receptor were transplanted in nude mice with metastasizing gastric cancer. After tumor growth (4-6 weeks) animals were randomly allocated to intraperitoneal 100 microg SC-1 (n=23) or 100 microg human IgM (n=23). One week later, animals were sacrificed and blood and bone marrow specimens were obtained. A nested RT-PCR for cytokeratin 20 (CK-20) from blood and bone marrow of mice was performed for detection of disseminated tumor cells. Animals receiving SC-1 had significantly fewer DTCs than did control animals (p=0.0011). None of the SC-1 mice had DTCs simultaneously in both blood and bone marrow versus four of the control animals (p=0.0363). The reduction of DTCs in SC-1 animals was due to reduction in bone marrow (p=0.032 compared to controls), but not in blood (p=0.1158). Treatment with SC-1 significantly reduced the number of DTCs in bone marrow in this animal model.

PAM-1, a natural human IgM antibody as new tool for detection of breast and prostate precursors

Early detection and differential analysis of premalignant lesions are very important for both prognosis and therapy of cancer patients. A good source of diagnostic tools is the natural antibody pool of humans. Tumor-specific antibodies can be established by using hybridoma technology. The fully human germline-coded monoclonal IgM antibody PAM-1 was isolated from a patient with a stomach carcinoma. PAM-1 reacts with a post-transcriptionally modified isoform of membrane receptor CFR-1 which is overexpressed on almost all epithelial cancers of all types and origins. The expression of CFR-1/PAM-1 on precancerous stages of breast and prostate cancer was analyzed by immunohistochemistry and compared with normal breast and prostate tissue as well as adenocarcinomas of both. In addition FACS analysis was performed to detect receptor expression on benign and malign prostate cells. 73 different tissue samples of prostate and breast precancerous stages and prostate and breast carcinomas were analysed for CFR-1/PAM-1 expression immunohistochemically. The CFR-1/PAM-1 receptor was expressed on nearly all precancerous stages and carcinomas while normal breast and prostate tissue showed negative results. These results were confirmed by FACS analysis showing a CFR-1/PAM-1 expression only on prostate carcinoma cells but not on benign prostate hyperplasia cells. The unique expression of this new CFR-1/PAM-1 receptor makes the PAM-1 antibody an ideal diagnostic and even therapeutic tool for precancerous and cancerous epithelial lesions of the breast and the prostate.

Production of a human monoclonal IgM directed against human cardiac myosin in a hollow-fiber bioreactor for Membrane Anion Exchange Chromatography one-step purification

Purification of human IgM monoclonal antibodies (MAbs) has proved to be difficult. Since IgM Mabs tend to bind strongly to a variety of resin support surfaces, the number of chromatographic steps used in the purification of these biomolecules should be minimized. Here we describe procedures developed for the optimal production and purification of the human monoclonal IgM B7, which specifically binds to the myosin heavy chain of human ventricular myocardium. This property makes this antibody potentially useful for the diagnosis of myocardial necrosis. Several chromatographic techniques were evaluated (size exclusion, ion exchange, affinity chromatography). The best results were obtained with anion exchange membrane chromatography using Sartobind Q15 (98% purity, 30% recovery). IgM production was improved by the hollow fiber technology which permitted the use of serum-reduced medium and an increase in antibody concentration to an average production of 300-400 microg/ml, compared to 20 microg/ml in flask culture. Several flow-rates were also evaluated, the optimal being 20 ml/minute for 30% of recovery. Importantly, the purified IgM molecule was able to bind to human myosin in ELISA and Western-blotting, thus allowing the IgM to be kept intact for further radiolabeling.

HMMC-1

The purpose of this research was to generate a human monoclonal antibody specific to gynecological cancers and to evaluate such an antibody as therapy for gynecological cancers. Transchromosomal KM mice were immunized with the human uterine endometrial cancer cell line SNG-S. Hybridomas were constructed between spleen cells from KM mice and mouse myeloma cells. Reactivity of the antibody was evaluated by immunohistochemistry of pathological specimens of gynecological cancers. Cytotoxicity of HMMC-1 against SNG-S cells was tested by in vitro cytotoxicity assays. The epitope of HMMC-1 was determined by transfection with a panel of glycosyltransferase cDNAs and by inhibition assays with chemically synthesized oligosaccharides. HMMC-1 is a human IgM monoclonal antibody that reacts positively with mullerian duct-related carcinomas with positive rates of 54.6% against uterine endometrial adenocarcinoma, 76.9% against uterine cervical adenocarcinoma, and 75.0% against epithelial ovarian cancer. HMMC-1 does not react with normal endometrium at proliferative or secretory phases, normal uterine cervix, or normal and malignant tissue from other organs, whereas it reacts weakly with the epithelium of the gall bladder and the collecting duct of the kidney. HMMC-1 exhibits antigen-dependent and complement-mediated cytotoxicity. Upon cotransfection with cDNAs encoding two glycosyltransferases required for fucosylated extended core 1 O-glycan, mammalian cells express HMMC-1 antigen. Finally, binding of HMMC-1 to SNG-S cells is inhibited by synthetic Fucalpha1-->2Galbeta1-->4GlcNAcbeta1-->3Galbeta1-->3GalNAcalpha1-octyl. These results indicate that HMMC-1 specifically recognizes a novel O-glycan structure. The unique specificity and cytotoxicity of HMMC-1 strongly suggest a therapeutic potential of this antibody.

Naturally Occurring Proteolytic Antibodies: SELECTIVE IMMUNOGLOBULIN M-CATALYZED HYDROLYSIS OF HIV gp120

We report the selective catalytic cleavage of the HIV coat protein gp120, a B cell superantigen, by IgM antibodies (Abs) from uninfected humans and mice that had not been previously exposed to gp120. The rate of IgM-catalyzed gp120 cleavage was greater than of other polypeptide substrates, including the bacterial superantigen protein A. The kinetic parameters of gp120 cleavage varied over a broad range depending on the source of the IgMs, and turnover numbers as great as 2.1/min were observed, suggesting that different Abs possess distinct gp120 recognition properties. IgG Abs failed to cleave gp120 detectably. The Fab fragment of a monoclonal IgM cleaved gp120, suggesting that the catalytic activity belongs to the antibody combining site. The electrophoretic profile of gp120 incubated with a monoclonal human IgM suggested hydrolysis at several sites. One of the cleavage sites was identified as the Lys(432)-Ala(433) peptide bond, located within the region thought to be the Ab-recognizable superantigenic determinant. A covalently reactive peptide analog (CRA) corresponding to gp120 residues 421-431 with a C-terminal amidino phosphonate diester mimetic of the Lys(432)-Ala(433) bond was employed to probe IgM nucleophilic reactivity. The peptidyl CRA inhibited the IgM-catalyzed cleavage of gp120 and formed covalent IgM adducts at levels exceeding a control hapten CRA devoid of the peptide sequence. These observations suggest that IgMs can selectively cleave gp120 by a nucleophilic mechanism and raise the possibility of their role as defense enzymes.

Prognostic effect of CD55SC-1 in gastric carcinoma (GC) and survival after treatment with the monoclonal antibody SC-1

4067 Background: SC-1 is a human monoclonal IgM antibody that targets CD55SC-1, a cell surface receptor specifically expressed on human GC cells, inducing apoptotic cell death and tumor cell regression in nude mice with no toxicity. The aim of this study was to examine whether CD55SC-1 expression is a prognostic tool in GC, and whether SC-1 confers a survival benefit in GC patients. Methods: Retrospective data from 126 CD55SC-1 positive and negative GC surgery-only patients from 1990–1997 was used to determine the prognostic ability of CD55SC-1. In an open-label, non-randomized study between 1997–2001, 51 CD55SC-1 positive GC patients received a single i.v. infusion of 10–30mg SC-1 24–48 hours before curative surgical (R0) resection. Data were compared to 19 CD55SC-1 negative GC patients who received only curative surgery between 1997–2001. Results: In the retrospective analysis, median survival of CD55SC-1 negative R0 patients was better than untreated CD55SC-1 positive R0 patients (93 months vs. 27 months); better UICC staging is associated with CD55SC-1 negative patients who are more associated with longer survival than CD55SC-1 positive patients (Cox proportional hazards, HR=2). In R0 resected patients after 1997, treatment with SC-1 increased survival at 2 years (77%) compared to CD55SC-1 negative untreated patients (63%). Conclusions: CD55SC-1 may be a prognostic factor in GC; an imbalance in UICC stage between CD55SC-1 positive and negative patients requires further data to confirm the prognostic ability of CD55SC-1, and may also indicate that CD55SC-1positive tumors are more aggressive. Treatment of CD55SC-1 positive GC patients with SC-1 increased 2-year survival compared to CD55SC-1 negative untreated patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration H3 Pharma, Inc.; OncoMab GmbH OncoMab GmbH OncoMab GmbH

Prognostic effect of CD55SC-1 in gastric carcinoma (GC) and survival after treatment with the monoclonal antibody SC-1

4067 Background: SC-1 is a human monoclonal IgM antibody that targets CD55SC-1, a cell surface receptor specifically expressed on human GC cells, inducing apoptotic cell death and tumor cell regression in nude mice with no toxicity. The aim of this study was to examine whether CD55SC-1 expression is a prognostic tool in GC, and whether SC-1 confers a survival benefit in GC patients. Methods: Retrospective data from 126 CD55SC-1 positive and negative GC surgery-only patients from 1990–1997 was used to determine the prognostic ability of CD55SC-1. In an open-label, non-randomized study between 1997–2001, 51 CD55SC-1 positive GC patients received a single i.v. infusion of 10–30mg SC-1 24–48 hours before curative surgical (R0) resection. Data were compared to 19 CD55SC-1 negative GC patients who received only curative surgery between 1997–2001. Results: In the retrospective analysis, median survival of CD55SC-1 negative R0 patients was better than untreated CD55SC-1 positive R0 patients (93 months vs. 27 months); better UICC staging is associated with CD55SC-1 negative patients who are more associated with longer survival than CD55SC-1 positive patients (Cox proportional hazards, HR=2). In R0 resected patients after 1997, treatment with SC-1 increased survival at 2 years (77%) compared to CD55SC-1 negative untreated patients (63%). Conclusions: CD55SC-1 may be a prognostic factor in GC; an imbalance in UICC stage between CD55SC-1 positive and negative patients requires further data to confirm the prognostic ability of CD55SC-1, and may also indicate that CD55SC-1positive tumors are more aggressive. Treatment of CD55SC-1 positive GC patients with SC-1 increased 2-year survival compared to CD55SC-1 negative untreated patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration H3 Pharma, Inc.; OncoMab GmbH OncoMab GmbH OncoMab GmbH

Lipoptosis: tumor-specific cell death by antibody-induced intracellular lipid accumulation.

A balanced lipid metabolism is crucial for all cells. Disturbance of this homeostasis by nonphysiological intracellular accumulation of fatty acids can result in apoptosis. This was proven in animal studies and was correlated to some human diseases, like lipotoxic cardiomyopathy. Some metabolic mechanisms of lipo-apoptosis were described, and some causes were discussed, but reagents, which directly induce lipo-apoptosis, have thus far not been identified. The human monoclonal IgM antibody SAM-6 was isolated from a stomach cancer patient by using the conventional human hybridoma technology (trioma technique). The addition of SAM-6 to tumor cells leads to an increase in the intracellular accumulation of neutral lipids, followed by tumor cell apoptosis. The antibody SAM-6 does not react with noncancerous human epithelial and fibroblastic cells, because the M(r) 140000 membrane molecule, recognized by the antibody, is specifically expressed on human malignant cells. The antibody is coded by the germ-line genes IgHV3-30.3*01 and IgLV3-1*01 and is a component of the innate immunity to cancer. In this article, we describe an antibody-induced tumor-specific cell death, named lipoptosis. This is, to our knowledge, the first description of this specific form of lipo-apoptosis as an antibody-mediated mechanism of tumor cell killing.

MRNA expression of AgSK1, an adenocarconoma-associated antigen, in tumor tissue of patients with colorectal cancer: Quantitative RT-PCR analysis

SK1, a human IgM monoclonal antibody recognizes the antigen, termed AgSK1 which was shown to be preferentially expressed by human adenocarcinomas, particularly human gastrointestinal malignancies. The aim of this study was to clarify the clinicopathological significance of AgSK1 mRNA expression in human colorectal cancer. Using a quantitative RT-PCR, we studied the mRNA expression level of AgSK1 in the resected specimen of 40 patients with colorectal cancer. We estimated the tumor tissue value (T-value), nontumorous tissue value (N-value), and the ratio of T-value to N-value (T/N Ratio). For further analysis, we compared these data with the clinicopathological features. In the status of lymph node metastases, pN positive status tended to have a higher T-value level of AgSK1 mRNA than pN negative status (P = 0.076). According to a mean T-value (8.032) or a mean T/N Ratio (1.549), we divided these patients into two groups, low expression group and high expression group. A high expression group showed a significantly higher frequency of positive lymph node metastases (T-value; P = 0.021, T/N Ratio; P = 0.024). AgSK1 mRNA expression in tumor tissue may become a useful marker for lymph node metastases and a malignant potential marker of colorectal cancer.

Intralesional radioimmunotherapy with Yttrium-90-labeled human monoclonal IgM in nude mice bearing human tumor xenografts.

Biodistribution studies demonstrate that intralesional administration of radiolabeled IgM results in high retention of radioactivity with little normal tissue uptake. This study examines the therapeutic potential of this modality. Nude mice bearing subcutaneous human head and neck squamous cell carcinoma xenografts were treated with single intralesional (IL) injections of tumor-reactive human monoclonal IgM (CR4E8) labeled with 25-394 microCi of yttrium-90 (90Y). Untreated mice, mice treated with IL unlabeled immunoconjugate or IL 90Y-aggregate, 160-400 microCi, served as controls. Mice were monitored for tumor growth and toxicity. Mice received 80 Gy per 100 microCi of 90Y-labeled IgM and 110 Gy per 100 microCi of 90Y-aggregate. All tumors treated with 90Y-labeled IgM responded. In mice that received > or = 100 microCi, tumors macroscopically disappeared within three weeks from treatment with seventy-six percent tumor-free at 216 days. Acute toxicities associated with high activity 90Y-labeled IgM and 90Y-aggregate were moist skin desquamation and reduced blood counts. Late radiation damage to connective tissue was observed in mice treated with > 100 microCi of 90Y-labeled IgM. Intralesional administration of 90Y-labeled IgM can ablate tumors in nude mice with modest acute or late toxicity. Further development of this modality for loco-regional therapy is warranted.

Expression of Y7 Cross‐Reactive Idiotope on Human IgM Molecules

In this paper we report data regarding the IgM Y7 cross‐reactive idiotope (CRIo) obtained by analysis of: 1) its V‐gene subgroup dependance, 2) the frequency of its expression on human monoclonal IgMs and IgM molecules from normal and pathological sera. Furthermore, comparison of epitopic repertoire and nature of binding of human monoclonal IgMs expressing Y7 CRIo was performed to confirm the natural antibody properties of these molecules. IgM isolated from sera of patient DJ (IgM DJ) which expresses the Y7 idiotope has been classified to VH3/VL2 subgroup. From ten IgMs tested only IgM from patient RD (IgM RD) has been shown to express Y7 idiotope. Y7+ human IgMs bound to ssDNA, lactic acid bacteria, mouse laminin, porcine thyroglobulin and mouse IgG. Higher percentage of the expression of Y7 CRIo was detected in the sera of patients suffering from autoimmune diseases such as lupus, rheumatoid arthritis and psoriasis vulgaris as well as in patients suffering from chronic infections of the lower urinary tract. Antigen binding repertoire and properties of Y7+ monoclonal IgM, frequency of Y7 expression on monoclonal IgMs and its concentration in normal and pathological sera indicate the important biological role of this CRIo within the immune system.

The Possible Role of Natural Idiotopes in Immune Memory

In this paper we report on the generation of Abs possessing specificities similar to those of Abs used in immunization, and on the generation of Id and anti-Id specificities in the sera of mice immunized with commensal bacterial antigens. The human monoclonal antibody IgM DJ (VH3/VL2) expresses natural antibody properties, natural idiotope (Y7), and specificity towards Lactic acid bacteria (LAB). When used in immunization it generates LAB-specific antibodies. Immunization with LAB, as detected in the presence of biotin-labelled mouse monoclonal anti-idiotopic antibodies Y7 and IgM DJ generates Abs1 and Abs2, respectively. These findings may imply that the recognition of bacterial motifs accords with the rules of idiotypic network theory. This theory, first proposed by Jerne in 1974 and often overlooked since, has been subject to change during the course of immunological research. Recent experiments concerning the recognition of bacterial motifs and natural memory in the immune system have inspired us in our attempt at explaining the possible role of natural Id in immune memory.

Protein Fv Produced during Viral Hepatitis Is an Endogenous Immunoglobulin Superantigen Activating Human Heart Mast Cells

Protein Fv, an endogenous protein produced in the liver, is released in biological fluids during viral hepatitis. Acute and chronic viral hepatitis can be associated with cardiovascular derangements. Protein Fv induced the release of histamine, tryptase and the de novo synthesis of prostaglandin D₂ and cysteinyl leukotriene C₄ from mast cells isolated from human heart tissue (HHMC). Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion. The maximal percent histamine secretion induced by protein Fv correlated (r_s = 0.60; p < 0.05) with that induced by anti-IgE, whereas there was no correlation between the release caused by proteins Fv and C5a. Preincubation of HHMC with protein Fv or anti-IgE caused complete cross-desensitization to subsequent challenge with heterologous stimulus. HHMC from which IgE had been dissociated no longer released histamine in response to anti-IgE and protein Fv. A human monoclonal IgE blocked both anti-IgE- and protein Fv-induced release. Three human monoclonal IgM V_H3⁺ inhibited protein-Fv-induced secretion of histamine from HHMC, whereas monoclonal IgM V_H6⁺ did not inhibit the release induced by protein Fv. Protein Fv acts as an endogenous immunoglobulin superantigen by interacting with the V_H3 domain of IgE to induce the release of mediators from HHMC.

Human monoclonal IgM antibodies with apoptotic activity isolated from cancer patients

Monoclonal antibodies are accepted as ideal adjuvant therapeutic reagents for all kinds of diseases. Polyvalent (cross-linking) and low-mutated IgM antibodies (less immunogenic) are believed to be the most effective weapons against cancer. The best sources for these types of antibodies are the cancer patients themselves. Using conventional hybridoma technology, not only are fully human monoclonal IgM antibodies isolated, but also new tumor-related targets can be identified using the same experimental approach. The resulting antibodies can be used directly for therapeutic purposes without further modulation and manipulation. This report describes five newly established human monoclonal IgM antibodies; antibody LM-1 that was isolated from a patient with lung cancer, antibodies PM-1 und PM-2 that were isolated from a patient with pancreatic cancer, and antibodies CM-1 and CM-2 which were isolated from a patient with colon carcinoma. The mainly germ-line encoded antibodies are specific for malignant tissues and show only restricted reactivity with healthy cells. When tested for in vitro functional activity, all five antibodies inhibit tumor cell proliferation of carcinoma cells by inducing apoptosis.

Nature's best weapons to fight cancer. Revival of human monoclonal IgM antibodies

The unique features of monoclonal antibodies (specificity, effectiveness, purity and unlimited reproducibility) make them ideal tools for the specific treatment of all kind of diseases. The third generation of monoclonal antibodies for the treatment of human diseases will be, after murine and "humanised" murine immunoglobulins, fully human antibodies. The best source of human monoclonal antibodies are the antibody pools of cancer patients themselves with the best technique for generating them being conventional human hybridoma technology. This technique, will generate human monoclonal antibodies which will not only define important new targets on cancerous tissue, but will also provide the necessary therapeutic human antibodies in the fight against cancer.