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PubMed2004

[Expression of antigen CD40 and survivin gene and their clinical implications in acute myeloid leukemia].

OBJECTIVE: To evaluate the expressions of CD40 antigen and anti-apoptosis gene survivin in acute myeloid leukemia (AML) and their clinical significance. METHODS: By using flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR), CD40 antigen and anti-apoptosis gene survivin mRNA were studied in 48 AML cases and their association with the clinical features of AML was analysed. RESULTS: (1) In the 48 AML cases, positive expression of CD40 antigen was found in 25 cases (52.1%) and positive expression of anti-apoptosis gene survivin mRNA in 35 cases (72.9%). (2) The incidence of splenomegaly, thrombocytopenia and hyperleukocytosis in CD40+ AML cases was significantly higher than those in CD40- AML ones (36.0% vs 8.7%), P=0.025; (72.0% vs 43.5%), P=0.045; (32.0% vs 4.4%), P=0.024. (3) There was no difference in the number of the expression of survivin mRNA between CD40+ AML cases and CD40- AML ones (20/25 vs 15/23) P=0.25, but the expression of survivin mRNA of both the groups was high than those of normal controls (20/25 vs 6/20), P=0.001; (15/23 vs 6/20), P=0.021. In the 48 AML cases the rate of the expression of CD40 antigen was less than those of anti-apoptosis gene survivin mRNA (52.1% vs 72.9%), P=0.041. (4) The complete remission (CR) rate in the survivin+ AML cases receiving chemotherapy was significantly less than that in the survivin- AML ones (31.4% vs 69.2%), P=0.018. CONCLUSIONS: The expression of CD40 antigen might be associated with some unfavorable clinical features of AML. The expression of anti-apoptosis gene survivin might be one of the reasons that AML have a lower CR rate, and it is one of the prognostic factors in AML.

Adolescent↗
PubMed1995

Expression of B7 (CD80) and CD40 antigens and the CD40 ligand in Hodgkin's disease is independent of latent Epstein-Barr virus infection.

Aim-To examine the expression of CD40 and B7 (CD80) antigens and the CD40 ligand in Hodgkin's disease.Methods-Antigen and ligand expression was studied in 17 cases of Hodgkin's disease using immunohistochemistry. The study included 11 cases of Hodgkin's disease in which latent Epstein-Barr virus (EBV) infection could be demonstrated within tumour cells by in situ hybridisation for the EBV encoded early RNAs (EBERs).Results-In all cases, irrespective of EBV status, Reed-Sternberg cells and their variants (HRS cells) showed strong expression of both B7 and CD40 antigens. CD40 ligand expression was not shown in HRS cells but was confined to a subset of small lymphocytes some of which were seen to be in intimate contact with HRS cells.Paraffin wax sections from a further 60 cases of Hodgkin's disease were examined for CD40 and EBER expression alone. The CD40 antigen was identified in HRS cells in all of these cases irrespective of EBER expression.Conclusions-As CD40 and B7 expression are features of professional antigen presenting cells, these results provide further evidence that HRS cells may have antigen presenting properties and that this may contribute to the characteristic recruitment and activation of non-malignant lymphocytes which is a feature of Hodgkin's disease. The ability of HRS cells to activate T(h) cells may in turn contribute to their own survival through the induction of the gp39/CD40 pathway.

Journal Article↗
PubMed1992

Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated through their antigen receptors or CD40 antigens.

The pan-T cell antigen CD5 has been shown to delineate two different mouse B cell subsets, originating from distinct progenitors. In man, on average, 30% of the tonsillar B cell pool expresses this antigen. In the present report, a detailed comparison of the CD5+ and CD5- B cell response to cytokines, following activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken. CD5+ B cells were positively selected by panning or by sorting from tonsils. Two-color immunofluorescence analysis performed on tonsillar B cell populations showed that CD5+ B cells displayed most of the phenotypic features of mantle zone B cells. CD5+ B cells could be stimulated for DNA synthesis by mitogenic concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti-IgM antibodies, immobilized anti-CD40 antibodies and phorbol 12-myristate 13-acetate (PMA). The growth-response of small dense CD5- B cells to these T cell-independent mitogens was comparable to that of CD5+ B cells, whereas the low-density, in vivo-activated, CD5- B cells were only marginally stimulated by Ig-cross-linking agents and PMA. Following ligation of sIg, both B cell subsets proliferated essentially in response to interleukin (IL)-2 and IL-4. When used in co-stimulation with immobilized anti-CD40 antibodies, IL-4 promoted growth of CD5+ and CD5- B cells, whereas IL-2 displayed only moderate stimulatory effects. CD5+ and CD5- B cells differentiated into Ig-secreting cells when they were co-cultured with SAC or cross-linked anti-CD40 antibodies and IL-2. However, IgM constituted the major component of the Ig response of CD5+ B cells, whereas high levels of IgG were secreted by CD5- B cells.

Antigens, CD↗
PubMed1997

Engagement of CD40 antigen with soluble CD40 ligand up-regulates peptide transporter expression and restores endogenous processing function in Burkitt's lymphoma cells.

Cells from the EBV-associated tumor, Burkitt's lymphoma (BL), are known to be highly inefficient at endogenous processing of class I-restricted CTL epitopes due to a consistent loss of peptide transporters (TAP) and MHC expression. We investigated the potential of CD40 engagement to up-regulate the expression of class I-processing genes and to enhance the immunogenicity of these malignant cells toward EBV-specific CTLs. Here we show that engagement of CD40 Ag with soluble CD40 ligand (CD40L) up-regulates TAP-1 and HLA class I expression on BL cells. More importantly, analysis of the Ag-processing function, using a recombinant vaccinia virus to transiently express the EBV nuclear Ags, revealed that CD40L-treated BL cells consistently processed endogenously synthesized viral Ags for recognition by HLA class I-restricted, virus-specific CTLs. These findings raise the possibility that CD40L treatment of tumor cells might be exploited in immunotherapeutic protocols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen.

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti-CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H-thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.

Adult↗
PubMed1994

The CD40 antigen and its ligand.

CD40 is an integral membrane protein found on the surface of B lymphocytes, dendritic cells, follicular dendritic cells, hematopoietic progenitor cells, epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is expressed on activated T cells, mostly CD4+ but also some CD8+ as well as basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome. Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the generation of factor-dependent long-term normal human B cell lines and the secretion of IgE following isotype switching. Addition of IL-10 results in very high immunoglobulin production with limited cell proliferation. IL-10 induces naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta permits the secretion of IgA2. Several evidences suggest that CD40-dependent activation of B cells is important for the generation of memory B cells within the germinal centers: (i) CD40 activated germinal center B cells cultured in the presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper-IgM syndrome characterized by lack of germinal centers in secondary lymphoid organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells are present in secondary follicles. Thymic epithelial cells, activated monocytes, and dendritic cells express CD40 antigen which may be involved in an enhanced cytokine production by these cells, allowing an amplification of T cell proliferation. Finally, as other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.

Amino Acid Sequence↗
PubMed1996

CD40 antigen is expressed by endothelial cells and tumor cells in Kaposi's sarcoma.

The CD40 antigen is a member of the tumor necrosis factor receptor/nerve growth factor receptor superfamily and is involved in cell proliferation, differentiation, and survival. Using different monoclonal antibodies, we found CD40 expression by immunohistochemistry on CD31- and CD34-positive Kaposi's sarcoma spindle cells in all tumors of 18 HIV-1 seropositive and 4 HIV-1 seronegative patients. Western blot analysis of tumor lysates detected a 48- to 50-kd glycoprotein corresponding to the CD40 antigen expressed by B lymphocytes. CD40 expression was also detectable in one of four cultures of spindle cells derived from Kaposi sarcoma tissue. Treatment of the CD40-positive spindle cells but not of the CD40-negative ones with interferon-gamma up-regulated CD40 surface expression. Besides on Kaposi sarcoma tumor cells, CD40 was distinctly present on vascular endothelial cells in areas within and adjacent to the tumors and in benign inflammatory lesions such as granulation tissue of HIV-1-negative patients. In contrast, CD34-negative endothelia of thin walled vessels, most likely lymphatics, were predominantly CD40 negative. Only faint or no CD40 expression was found on endothelial cells in normal skin. We conclude from our data that expression of the CD40 antigen by endothelial cells is up-regulated during tissue inflammation. As signaling through CD40 is able to increase cell survival, expression of CD40 by Kaposi sarcoma tumor cells might play an important role in the pathogenesis of this neoplasm.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The role of the CD40 antigen on malignant B cells.

An increasing amount of literature has been published concerning the interaction of the CD40 antigen and its ligand with regard to normal B cell ontogeny. In this review, an overview of the CD40 antigen and the CD40 ligand is given, focussing on their possible role in B cell malignancies. Data on the expression of the CD40 antigen on various B cell malignancies (acute and chronic leukemias, non-Hodgkin's lymphoma and multiple myeloma) are presented. The recently developed novel culture "CD40 system" is described. This system is a powerful tool used to culture normal B cells, but also most malignant B cells. We demonstrate in addition a more prominent role of the human Fc receptor presenting murine fibroblasts in the "CD40 system", especially in relation to cultured plasma cells. Finally, some important applications of the "CD40 system" are also summarized.

Animals↗
PubMed1996

Expression of the CD40 antigen on normal endothelial cells and in benign and malignant tumours of vascular origin.

CD40, a member of the nerve growth factor/tumour necrosis factor-receptor family, is expressed on endothelial cells in situ and in tissue culture. It is functionally involved in the regulation of the expression of adhesion molecules in these cells. In the current study we investigated the expression of CD40 on the endothelia of normal fetal and adult human tissues, as well as in the stroma of various neoplasms and in different inflammatory tissue reactions. By immunohistochemistry, endothelia were negative or only weakly positive for CD40 in all normal adult and most fetal organs studied. In contrast, endothelial cells of fetal and embryonic lungs, kidneys and larger vessels consistently expressed the CD40 antigen. Strong expression of CD40 on endothelial cells of blood vessels but not of lymphatic vessels was found in inflammatory reactions. In 65 tumours of vascular origin we found moderate to strong expression of CD40 in all of four juvenile proliferating capillary haemangiomas and 11 lobular capillary haemangiomas of adults. Senile and cavernous haemangiomas as well as lymphangiomas were negative or exhibited only weak CD40 reactivity. Weak to moderate CD40 expression was found in five of eight malignant neoplasms of endothelial origin. Our finding that the CD40 antigen is present on only a minority of normal endothelial cells, whereas strong staining can be detected on the majority of endothelial cells in inflammatory processes, complements previous reports which suggest that this surface receptor plays an important role in tissue inflammation. The heterogeneous pattern of expression in malignant endothelial neoplasms argues against a major role for CD40 in the pathogenesis of these tumours. Its consistent presence in juvenile and lobular capillary haemangiomas suggests rather the involvement of CD40 in the development and/or progression of these benign vascular proliferations.

Adult↗
PubMed1996

Stimulation of human lymphocyte proliferation and CD40 antigen expression by phosphorothioate oligonucleotides complementary to hepatitis B virus genome.

We have studied the proliferation and CD40 antigen expression of lymphocytes, and the cytotoxicity to monocytes, of antisense phosphorothioate oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA (sequence I) and the X gene (sequence II) in patients with chronic hepatitis B. The oligo sequence I stimulated proliferation of both T and, to a lesser extent, B cells. The percentage of cells expressing CD40 in T and B cell co-cultures increased from 4.2% to 13.8% after oligo stimulation in patients, while it increased form 4.7% to 48.6% in healthy controls. The sense sequence (sequence III) of the X gene also enhanced the expression of CD40 antigen in patients with hepatitis B. The proportion of CD40 cells (26%) in a resting B-cell preparation from hepatitis B patients decreased to zero after a 5-day culture with sequence I, but IgG levels in the culture supernatant increased. The cytotoxic properties of monocytes were not influenced by the oligos. These findings indicate that antisense oligos against hepatitis B virus (HBV) have mitogenic effects on the proliferation of human lymphocytes in a non-specific manner and may activate T cells to express CD40 antigen.

Adult↗
PubMed1993

Expression of a 32-kDa ligand for the CD40 antigen on activated human T lymphocytes.

To identify the ligand(s) of the human CD40 antigen, a cDNA encoding the extracellular domain of the CD40 antigen was fused to a cDNA encoding the constant region (Fc) of human IgG1. The CD40-Fc fusion protein was able to specifically bind to CD4+ and various CD8+ T cell clones activated with immobilized anti-CD3. The 125I-labeled CD40-Fc fusion protein bound anti-CD3 activated CD4+ T cell clone (MT9) with an equilibrium dissociation constant (Kd) of 10-20 nM. The human CD40-binding protein expressed on the cell surface of activated T lymphocytes is a monomeric protein of approximately 32 kDa. Minor components of 29 kDa and 17 kDa were also detected. A small proportion of CD4+ and CD8+ blood mononuclear T cells activated by anti-CD3 expressed the CD40 ligand but its detection was best observed following depletion of B cells. Addition of B cells to purified T cells abolished the binding of CD40-Fc obtained after anti-CD3 activation.

Antigens, CD↗
PubMed1996

Proliferation of precursor B-lineage acute lymphoblastic leukaemia by activating the CD40 antigen.

No reliable culture system exists for B-lineage acute lymphoblastic leukaemia (ALL). Recently we found that many different mature B-cell malignancies proliferate upon stimulation via the CD40 antigen, and this led us to investigate whether a similar CD40 activation on ALL cells could also induce proliferation. First, we measured CD40 expression in 21 ALL cases; all were CD40+, although mostly weak. Next, we triggered the CD40 antigen by anti-CD40 antibodies and by a CD40 ligand-expressing cell line. In addition, we measured the influence of IL-3, IL-4 and IL-7 with and without these stimuli. In 8/10 cases proliferation, measured by 3H-thymidine incorporation, could be induced after CD40 crosslinking, especially in the presence of IL-3. Stimulation via the CD40 ligand was more successful than using crosslinked anti-CD40 antibodies. IL-4 inhibited the spontaneous proliferation found in three cases, but stimulated proliferation after CD40 crosslinking. IL-7 did not contribute to proliferation. Morphology, immunophenotyping and surface marker analysis, combined with DNA flow cytometry confirmed that the proliferation found could be ascribed to the ALL cells. In conclusion, B-lineage ALL cases are CD40+, and many can be cultured using CD40 stimulation and IL-3.

Burkitt Lymphoma↗
PubMed1990

Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells.

Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B-lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence-activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS-sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.

Antibodies, Monoclonal↗
PubMed1998

Triggering of CD40 antigen inhibits fludarabine-induced apoptosis in B chronic lymphocytic leukemia cells.

We analyzed the effect of CD40 triggering on the fludarabine-induced apoptosis of B chronic lymphocytic leukemia (B-CLL) cells. Peripheral blood samples obtained from 15 patients were incubated with fludarabine in the absence or the presence of the anti-CD40 monoclonal antibody (MoAb) G28-5. In 12 patients a significant proportion of apoptotic cells, ranging from 22% to 38% (mean +/- SE: 28.5 +/- 1.6), were detected after 3 days of culture. In 9 of these samples, the addition of G28-5 reduced apoptosis by at least 30.1% and by 57.1% +/- 7.8% on average (P = .0077). Because the CD40 antigen activates NF-kappaB/Rel transcription factors in B cells, and NF-kappaB/Rel complexes can inhibit cell apoptosis, we investigated whether the antiapoptotic effect of G28-5, in our system, could be related to modulation of NF-kappaB/Rel activity. As expected, B-CLL cells displayed significant levels of nuclear NF-kappaB/Rel activity; p50, RelA, and c-Rel components of the NF-kappaB/Rel protein family were identified in these complexes. After exposure to fludarabine, NF-kappaB/Rel complexes were decreased in the nuclei. The addition of G28-5 upregulated the NF-kappaB/Rel levels. To determine the involvement of NF-kappaB/Rel activity in the G28-5-mediated inhibition of apoptosis, we blocked the transcription factor with a decoy oligonucleotide, corresponding to the NF-kappaB/Rel consensus sequence. Cells incubated with the anti-CD40 MoAb in the presence of the decoy oligonucleotide but not a control oligonucleotide displayed a complete impairment of the G28-5 antiapoptotic effect, indicating that NF-kappaB/Rel activity was required for the inhibition of apoptosis. These results suggest that CD40 triggering in vivo could counteract the apoptotic effect of fludarabine on B-CLL cells and that its neutralization, or the use of NF-kappaB/Rel inhibitors, could improve the therapeutic effect of fludarabine.

Antibodies, Monoclonal↗
PubMed1992

Activated human T cells express a ligand for the human B cell-associated antigen CD40 which participates in T cell-dependent activation of B lymphocytes.

To identify the ligand for the B cell-associated antigen CD40, we constructed a chimeric immunoglobulin molecule where the extracellular portion of the CD40 protein replaced the normal immunoglobulin variable region. No binding was detected on resting peripheral blood T cells. However, following T cell activation with phorbol esters and ionomycin, the chimeric protein bound specifically to activated human T cells and precipitated a 35-kDa protein from such cells. The induction of the CD40 ligand was detectable on the cell surface after 1 h, with maximal expression after 8 h of stimulation. The T cells expressing CD40 ligand were predominantly CD4 positive, although a proportion of CD8-positive cells also expressed the protein. There was no particular correlation with CD45 phenotype. Finally, we found that soluble CD40 inhibited T-dependent B cell proliferation. The results are discussed in the context of cognate interactions between B and T cells.

Adult↗
PubMed1995

Functional expression of CD40 antigen on human epidermal Langerhans cells.

It is now well established that interactions of CD40 on the B cells, along with its ligand (CD40-L) on the T cells, regulate B cell proliferation and differentiation. However, the functional significance of CD40 expression on cells known for most efficient Ag-presenting function, i.e., dendritic cells, is not so clear. In this study, we demonstrate that CD40 is expressed on human dendritic Langerhans cells (LC) freshly isolated from epidermis. Using CD40-L transfected cells, CD40 triggering was found to enhance LC viability when cultured and to result in phenotypic alterations. Thus, a 2-day CD40 activation induced up-regulation of CD54 and CD86 at the LC surface, while it did not significantly affect the levels of HLA-DR, CD1a, CD58, and CD80 expression. These phenotypic changes correlate with enhanced LC allostimulatory property, as shown by the use of paraformaldehyde-fixed LC. Furthermore, mAbs against CD40, as well as CD40-L, strongly inhibit the primary T cell response to allogeneic LC. Collectively, these data support a role for CD40/CD40-L pair in the development of normal T cell functions.

Binding Sites, Antibody↗
PubMed1995

Activity of a single-chain immunotoxin that selectively kills lymphoma and other B-lineage cells expressing the CD40 antigen.

We have constructed anti-CD40 immunotoxins consisting of the single chain Fv (sFv) region of the anti-human CD40 mAb G28-5 fused to a truncated form of Pseudomonas exotoxin, PE40. CD40 is an integral membrane glycoprotein found on the surface of B-lineage cells, including lymphomas and leukemias, as well as certain carcinomas. Two forms of the immunotoxin were constructed, one with the light chain variable (VL) region of the sFv preceding the heavy chain variable region (VH) [G28-5 sFv(VL-VH)-PE40] and the second with the sFv in the opposite orientation [G28-5 sFv(VH-VL)-PE40]. Although both forms of G28-5 sFv-PE40 specifically bound to CD40 in ELISAs, the binding of G28-5 sFv(VL-VH)-PE40 was > 10-fold higher. A number of malignant B- and T-cell lines were screened for CD40 expression and susceptibility to G28-5 sFv(VL-VH)-PE40. All of the B-lineage cells tested were CD40 positive and sensitive to the anti-CD40 immunotoxin, with EC50s ranging from 2.5-70 ng/ml, whereas none of the T cell leukemias or lymphomas were antigen positive or were affected by the immunotoxins. Consistent with the antigen-binding results, the VL-VH immunotoxin was > 10-fold more cytotoxic than the VH-VL immunotoxin. The anti-CD40 single-chain immunotoxin fusion protein G28-5 sFv(VL-VH)-PE40 represents a potent and specific cytotoxic agent for the elimination of normal and transformed B-lineage cells expressing CD40.

ADP Ribose Transferases↗