Active Immunotherapy for Acute Lymphoblastic Leukæmia

Mathé, G; Amiel, J. L.; Schwarzenberg, L; Schneider, M.; Cattan, A; Schlumberger, Jean; Hayat, M.; Vassal, F. de

doi:10.1016/s0140-6736(69)92648-8

Cited by 582 publications

(119 citation statements)

References 6 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…The clinical application of active immunotherapy to human cancer is now about 30 years old, 17 an awkward age for a man or for an idea. Immunotherapy no longer generates the enthusiasm and optimism of its youth, but it has not matured sufficiently to takes its place in the conceptual framework of human tumor biology.…”

Section: Discussionmentioning

confidence: 99%

Treatment of metastatic melanoma with autologous, hapten‐modified melanoma vaccine: Regression of pulmonary metastases

et al. 2001

View full text Add to dashboard Cite

Key words: melanoma; vaccine; immunotherapy; autologous; cyclophosphamideStudies performed and published over the past 30 years have made it clear that immunizing a tumor-bearing patient to his or her own tumor cells is exceedingly difficult. An appealing explanation for this difficulty is that tumor antigens are weakly immunogenic and often induce tolerance, i.e., paralysis of the immune response, rather than effective immunity. 1 Fortunately, advances in basic immunology have disclosed a number of ways of breaking immunologic tolerance. One way is the judicious use of cytotoxic drugs. In 1967, Maguire and Ettore 2 made the surprising discovery that administration of cyclophosphamide to animals prior to an immunization caused the cell-mediated immune response to be augmented rather than suppressed. We have shown that this phenomenon applies to cancer-bearing humans as well. Thus, the administration of low-dose (300 mg/m 2 ) cyclophosphamide prior to an immunization with autologous tumor cells greatly increased the development of cell-mediated immunity to those cells. 3 A second approach to circumventing tolerance is the use of haptens-small molecules that are incapable of inducing an immune response unless they are coupled to a larger molecule. Coupling of a hapten to a protein, i.e., hapten modification, often results in the induction of an immune response to the protein that would otherwise not be possible. For example, Weigle, 4 in a series of now classic experiments, immunized mice with hapten-modified thyroglobulin. This resulted in the induction of an immune response not only to the hapten-modified thyroglobulin, but also to unmodified, i.e., native, thyroglobulin and produced autoimmune thyroiditis. A similar phenomenon was observed more recently by Neurath et al. 5 They found that application of the hapten dinitrophenyl to the colonic mucosa of mice resulted in the development of an autoimmune colitis, similar to human ulcerative colitis. Initially, these mice developed cellular immunity to the haptenmodified mucosa. However, as the chemically modified mucosa cells were shed, a potent immune response to the normal, unmodified mucosa developed, which led to the autoimmune pathology.The immunologic basis of these interesting phenomena is now clear: there are T lymphocytes generated by immunization with hapten-modified cells that are reactive to both modified and unmodified cells. For example, class I MHC-restricted T-cell clones generated from mice immunized with TNP-modified syngeneic lymphocytes respond to MHC-associated, TNP-modified "self" peptides. Furthermore, some TNP-reactive clones respond to certain MHC-binding, unmodified peptides as well. 6 These observations in animal models provide a strong rationale for a human cancer vaccine consisting of autologous tumor cells modified with a hapten, DNP, preceded by the administration of low-dose cyclophosphamide. We have observed that administration of DNP vaccine to patients with metastatic melanoma induces a unique reaction-the development of inflamma...

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment of metastatic melanoma with autologous, hapten‐modified melanoma vaccine: Regression of pulmonary metastases

et al. 2001

View full text Add to dashboard Cite

show abstract

“…[6][7][8] In transplantable animal tumor models, bacteria such as Clostridium, Corynebacterium, BCG and Salmonella, as well as Vaccinia and Newcastle viruses, have been evaluated for their selective anti-tumor properties. 9,10 Bifodobacterium, Clostridium and Salmonella have all been shown to somehow preferentially replicate within solid tumors when injected from distal sites.…”

Section: Introductionmentioning

confidence: 99%

Anti-tumor effects of the bacterium caulobacter crescentus in murine tumor models

Bhatnagar

Awasthi²,

Nomellini³

et al. 2006

Cancer Biology & Therapy

View full text Add to dashboard Cite

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10 7 cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.

show abstract

“…Dotychczas jeszcze żadna metoda nieswoistej czynnej immunoterapii nie znalazła trwałego miejsca w rutynowej praktyce klinicznej. Początkowe zachęcające wyniki badań na zwierzętach oraz pojedyncze korzystne efekty u ludzi w ostrej białaczce limfoblastycznej [54] nie znalazły potwierdzenia w kolejnych badaniach klinicznych, zwłaszcza prospektywnych i z randomizacją [55]. Długoletnie badania kliniczne obejmujące duże, liczące ponad tysiąc osób grupy chorych na raka jelita grubego, którzy byli leczeni przy uży-ciu BCG, zakończyły się niepowodzeniem [56][57][58].…”

Section: Nieswoista Czynna Immunoterapiaunclassified

Immunotherapy of cancer and perspectives of its development

Mackiewicz¹,

Maćkiewicz²

2010

View full text Add to dashboard Cite

Active Immunotherapy for Acute Lymphoblastic Leukæmia

Cited by 582 publications

References 6 publications

Treatment of metastatic melanoma with autologous, hapten‐modified melanoma vaccine: Regression of pulmonary metastases

Treatment of metastatic melanoma with autologous, hapten‐modified melanoma vaccine: Regression of pulmonary metastases

Anti-tumor effects of the bacterium caulobacter crescentus in murine tumor models

Immunotherapy of cancer and perspectives of its development

Contact Info

Product

Resources

About