Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung.

Ziegler, L. D.; Palazzolo, Paulette; Cunningham, Joan E.; Janus, M; Itoh, Kyogo; Hayakawa, Kazuhiro; Hellström, Ingegerd; Hellström, Karl Erik; Nicaise, Claude; Dennin, R

doi:10.1200/jco.1992.10.9.1470

Cited by 29 publications

(3 citation statements)

References 12 publications

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“…As a result, there is now increasing interest in the use of low-dose IL-2 to enhance the efficacy of monoclonal antibody (mAb) therapy. Some such trials have already been performed [50,51], although the IL-2-dosing regimens used in those studies were chosen on the basis of previous IL-2 trials and not with the intent of using the agent in a more physiological way. Our group is performing a clinical trial using the mAb cG250, which recognizes an antigen expressed in most clear cell-renal cell carcinomas [52] in combination with low-dose IL-2 given continuously for 6 weeks (trial LUD 00 -010).…”

Section: Cytokinesmentioning

confidence: 99%

Rational approaches to human cancer immunotherapy

Davis

Jefford

Parente

et al. 2003

Journal of Leukocyte Biology

112

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Over most of the 20th century, immunotherapy for cancer was based on empiricism. Interesting phenomena were observed in the areas of cancer, infectious diseases, or transplantation. Inferences were made and extrapolated into new approaches for the treatment of cancer. If tumors regressed, the treatment approaches could be refined further. However, until the appropriate tools and reagents were available, investigators were unable to understand the biology underlying these observations. In the early 1990s, the first human tumor T cell antigens were defined and dendritic cells were discovered to play a pivotal role in antigen presentation. The current era of cancer immunotherapy is one of translational research based on known biology and rationally designed interventions and has led to a rapid expansion of the field. The beginning of the 21st century brings the possibility of a new era of effective cancer immunotherapy, combining rational, immunological treatments with conventional therapies to improve the outcome for patients with cancer.

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Section: Cytokinesmentioning

confidence: 99%

Rational approaches to human cancer immunotherapy

Davis

Jefford

Parente

et al. 2003

Journal of Leukocyte Biology

112

View full text Add to dashboard Cite

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“…The tumor-associated antigen L6 (TAL6), is a tumor-specific antigen which is a distant member of the transmembrane-4 superfamily (TM4SF) and is often overexpressed in human lung, breast, and colon cancer tissues but not in normal tissues [ 3 – 5 ]. Antibody-based immunotherapy against membrane TAL6 protein was used to treat breast cancer in clinical studies [ 6 – 12 ], but the therapeutic effects were limited. Several strategies are used to improve immunotherapy for cancer treatment such as induction of cytotoxic T-cells (CTL) responses to lung cancer antigens [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model

Sher

Chen

et al. 2015

Oncotarget

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Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.

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“…In previous decades, both L6 and chimeric L6 (human-mouse) were conjugated with or without radioisotopes to treat breast cancer. [2][3][4][5][6][7][8] However, a phase I clinical study in patients with recurrent breast cancer using murine monoclonal antibody L6 produced only temporary remissions. 6 Similarly, a patient with aggressive, locally advanced breast cancer who was injected intravenously with radiolabeled I-131 chimeric L6 showed a partial response with transiently decreased tumor size.…”

mentioning

confidence: 99%

A Novel HLA-A2–restricted CTL Epitope of Tumor-associated Antigen L6 can Inhibit Tumor Growth In Vivo

Huang

et al. 2012

Journal of Immunotherapy

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Vaccines utilizing cytotoxic T lymphocyte (CTL) epitopes are promising for the treatment of cancer and chronic infectious diseases. Tumor-associated antigen L6 (TAL6) is overexpressed in some epithelial cancer cells. In this report, we detected TAL6 expression in breast cancer tissue using quantitative reverse-transcriptase-polymerase chain reaction. We found that >80% of breast tumor tissue highly expressed TAL6 compared with adjacent normal breast tissue. To identify CTL epitopes from TAL6, we synthesized 18 peptides for HLA-A2-binding assay based on the MHC-binding motif using 4 computer prediction programs. Positive binders identified by ELISA were immunized in HLA-A2 transgenic (A2 Tg) mice. Two peptides, peptide 2 and peptide 5, induced T-cell responses in A2 Tg mice. To confirm whether these peptides could be processed and presented to induce T-cell responses in vivo, A2 Tg mice were immunized with plasmid DNA encoding TAL6. We found that both peptides 2 and 5 stimulated splenocytes from TAL6-immunized mice to secrete interferon-γ. However, only peptide 5 could induce expression of the cytolytic molecule CD107a on CD8+ T cells after immunization. Furthermore, peptide 5-immunized A2 Tg mice could inhibit the growth of TAL6-positive tumors (EL4/TAL6/HLA-A2) in A2 Tg mice but not in wild-type mice. These results demonstrate that the TAL6-derived CTL epitope could induce HLA-A2-restricted immunity against TAL6-expressing tumor cells.

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Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung.

Abstract: L6 and SC IL-2 were well tolerated in the majority of patients when given in the outpatient setting. In view of the clinical efficacy of this combination, more phase II trials are warranted.

Cited by 29 publications

References 12 publications

Rational approaches to human cancer immunotherapy

Rational approaches to human cancer immunotherapy

A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model

A Novel HLA-A2–restricted CTL Epitope of Tumor-associated Antigen L6 can Inhibit Tumor Growth In Vivo

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