Phase I Study of Monoclonal Antibody-Ricin A Chain Immunoconjugate Xomazyme-791 in Patients with Metastatic Colon Cancer

LoRusso, Patricia; Lomen, Pavel L.; Redman, Bruce G.; Poplin, Elizabeth; Bander, J. J.; Valdivieso, M.

doi:10.1097/00000421-199508000-00008

Cited by 34 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this trial, reported in 1989 and 1995, all patients showed very high levels of HAMA and HARA [140]. Overall, no antitumor activity was detected [141]. No further trials were conducted.…”

Section: Xomazyme-791 (79it/36-rta)mentioning

confidence: 93%

Antibody-Based Immunotoxins for the Treatment of Cancer

Becker

Benhar

2012

Antibodies

View full text Add to dashboard Cite

Antibody-based immunotoxins comprise an important group in targeted cancer therapeutics. These chimeric proteins are a form of biological guided missiles that combine a targeting moiety with a potent effector molecule. The targeting moiety is mostly a monoclonal antibody (MAb) or a recombinant antibody-based fragment that confers target specificity to the immunotoxin. The effector domain is a potent protein toxin of bacterial or plant origin, which, following binding to the target cells, undergoes internalization and causes cell death. Over time and following research progression, immunotoxins become better fitted to their purpose, losing immunogenic fragments and non-specific targeting moieties. Many immunotoxins have gone through clinical evaluation. Some of these have been shown to be active and work is progressing with them in the form of further clinical trials. Others, mostly developed in the previous century, failed to generate a response in patients, or even caused undesired side effects. This article reviews the antibody and protein-toxin based immunotoxins that were clinically evaluated up to the present day.

show abstract

“…In this trial, reported in 1989 and 1995, all patients showed very high levels of HAMA and HARA [140]. Overall, no antitumor activity was detected [141]. No further trials were conducted.…”

Section: Xomazyme-791 (79it/36-rta)mentioning

confidence: 93%

Antibody-Based Immunotoxins for the Treatment of Cancer

Becker

Benhar

2012

Antibodies

View full text Add to dashboard Cite

show abstract

“…However, there are major drawbacks to the long-term use of monoclonal antibodies, murine, chimeric or human, which include a variable degree of immunogenicity and major costs, $12 -15 000 p.a. (d7 -9000) (Dillman et al, 1994;LoRusso et al, 1995;Philpott et al, 1995). TNF autovaccination is an alternative, novel approach that circumvents the problem of immunogenicity and cost of nonautologous antibodies.…”

mentioning

confidence: 99%

TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model

et al. 2004

View full text Add to dashboard Cite

TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (Po0.01) and size of metastases (Po0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer.

show abstract

“…Toxicity of ricin is expressed as its ability to chemically inactivate the eukaryotic ribosome by hydrolysis of a single adenine base (A4324) on the sarcin-ricin loop (SRL) of the 28S rRNA of the large subunit. This leads to loss of ribosomal activity and finally results in cell and/or tissue death (Endo and Tsurugi, 1987;Endo et al, 1988).Ricin A chain has been long reported to be a potential drug for various cancers, including leukemia, Hodgkin's diseases, breast cancer, cervical cancer and melanoma (Ghosh et al, 2013;LoRusso et al, 1995;Spitler, 1986;Spitler et al, 1987;Tyagi et al, 2015). However, other previous reports have shown that ricin B chain and total ricin also have antitumor activities in cervical cancer (Sadraeian et al, 2013;Liao et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Beside its toxic effects, ricin is also considered to have potential benefit in the treatment of a variety of cancers, including leukemia, breast cancer, cervical cancer and melanoma (Ghosh et al, 2013;LoRusso et al, 1995;Spitler, 1986;Spitler et al, 1987;Tyagi et al, 2015). Ricin A chain (but not ricin B chain and/or total ricin), as an immunotoxin conjugated with antibody, has been evaluated for melanoma treatment (Ghosh et al, 2013;LoRusso et al, 1995;Spitler, 1986;Spitler et al, 1987;Tyagi et al, 2015).…”

Section: Potential Of Total-ricin As An Anti-cancer Agentmentioning

confidence: 99%

“…Ricin A chain (but not ricin B chain and/or total ricin), as an immunotoxin conjugated with antibody, has been evaluated for melanoma treatment (Ghosh et al, 2013;LoRusso et al, 1995;Spitler, 1986;Spitler et al, 1987;Tyagi et al, 2015). In recent years, the application of nanotechnology, such as the use of robust nanoparticle carriers for drug delivery to target cancer cells, has been rapidly developing.…”

Section: Potential Of Total-ricin As An Anti-cancer Agentmentioning

confidence: 99%

See 1 more Smart Citation

Effects of ricin extracted from seeds of the castor bean (ricinuscommunis) on cytotoxicity and tumorigenesis of melanoma cells

Trung¹,

Tho²,

Dung³

et al. 2016

Biomed Res Ther

View full text Add to dashboard Cite

Abstract-Ricin has been reported as a potential therapeutic agent for the treatment of various cancers due to its potency. In this study, we succeeded in isolating and purifying total ricin from seeds of the castor bean (ricinus communis) from Vietnam. We also revealed that total ricin showed strong cytotoxicity against melanoma cells; IC50 at 48h was 34.1 ng/mL for SKMEL28 cells and 5.2 ng/mL for HaCaT cells. We examined the ability of total ricin to inhibit tumorigenesis of SKMEL28 cells in vitro. At low concentrations (< 3ng/mL)total ricin did not cause death of HaCaT or SKMEL28 cells but strongly reduced the size of SKMEL28 tumor colonies formed in soft agar. The effect of ricin on tumorigenesis was also confirmed by apoptotic and immunoblot analyses. Our results showed that treatment with total ricin (3 ng/mL) resulted in decreased ERK and p-ERK expression in SKME28 cells but did not affect expression levels of thosegenes in HaCaT cells. We showed that, although ricin at 1 and 3 ng/mLdid not induce apoptosis of HaCaT cells, it significantly increased apoptosis of SKMEL28 up to 1.4 folds and 2.1 folds, respectively. The results from our study suggest that although ricin is listed as one of the most poisonous substances in nature, it has potential to be used as a drug for melanoma treatment.

show abstract

Phase I Study of Monoclonal Antibody-Ricin A Chain Immunoconjugate Xomazyme-791 in Patients with Metastatic Colon Cancer

Cited by 34 publications

References 0 publications

Antibody-Based Immunotoxins for the Treatment of Cancer

Antibody-Based Immunotoxins for the Treatment of Cancer

TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model

Effects of ricin extracted from seeds of the castor bean (ricinuscommunis) on cytotoxicity and tumorigenesis of melanoma cells

Contact Info

Product

Resources

About