Lung Cancer Immunotherapy

Raez, Luis E.; Fein, Steven; Podack, Eckhard R.

doi:10.3121/cmr.3.4.221

Cited by 65 publications

(50 citation statements)

References 55 publications

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“…The working hypothesis is that the peptide mimics of mycobacterial antigens, particularly the nonprotein ones, would be useful as diagnostic agents. Moreover, since mycobacterial antigens are known to be immunomodulators (7,8), in addition to serving as diagnostic tools, such peptide mimics could be useful for therapeutic purposes, such as for the treatment of cancer (42). This is one of the first reports in which phage display tools have been used to identify mimotopes of mycobacterial antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Immunomodulation is an important option in the prevention of many diseases, such as cancer (57). The use of mycobacteria for the treatment of tuberculosis and certain forms of cancer is well known (42,51,55). Although the precise mechanisms of action are probably not known, it is most likely that modulation of cytokine responses is a key to such immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Specific and Randomly Derived Immunoactive Peptide Mimotopes of Mycobacterial Antigens

Sharma

Saha

Bhattacharjee

et al. 2006

Clin Vaccine Immunol

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The mycobacterial cell surface contains complex nonprotein antigens that are highly immunoactive in nature. However, these antigens are chemically heterogeneous and structurally complex, thereby limiting their applications. To identify their peptide mimotopes, phage-displayed peptide libraries Ph.D.-7 and Ph.D.-12 were panned on either defined template, monoclonal antibody (MAb) CS-35 against lipoarabinomannan (LAM), or a polyclonal rabbit immune serum reactive against whole cells of Mycobacterium bovis BCG. Panning on anti-LAM MAb CS-35 yielded two confirmed mimotopes of LAM, a 7-mer and a 12-mer, whereas panning on polyclonal serum yielded a large repertoire of mimotopes reactive against sera from BCG-immunized rabbits, one of which turned out to have the same sequence as the 7-mer LAM mimotope. The dissociation constant of the interaction between MAb CS-35 and a synthetic peptide corresponding to the 7-mer LAM mimotope was determined to be 7.55 M. Dot blot assays were performed with peptides corresponding to the two LAM mimotopes to evaluate their diagnostic potential. Both peptides gave discernibly higher signals with a panel of tuberculosis (TB) patient sera than with sera from healthy controls. The peptides were also found to stimulate the release of tumor necrosis factor alpha and interleukin-12 cytokines in the J774A.1 cell line and primary bone marrow-derived macrophages, indicating that they may have immunomodulatory potential. The present study demonstrates that peptide mimotopes of known and unknown mycobacterial antigens could be isolated by using subtractive phage display techniques and that these peptides could have potential applications in areas such as TB diagnostics and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Specific and Randomly Derived Immunoactive Peptide Mimotopes of Mycobacterial Antigens

Sharma

Saha

Bhattacharjee

et al. 2006

Clin Vaccine Immunol

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“…Although BRMs such as interferons, interleukins, and bacille Calmette-Guerin abound, they have not been found helpful in some types of cancers-lung cancer, for example. The search for an effective lung cancer immunotherapy agent continues, but thus far, the answer remains elusive 20 . In Japan, PSK research involves primarily cancers of the stomach, colon and rectum, esophagus, nasopharynx, and lung [nonsmall-cell (NSCLC) types] and the human leukocyte antigen B40-positive breast cancer subset 7 .…”

Section: Clinical Evidencementioning

confidence: 99%

“…Longterm survival in certain high-prevalence cancers, even in the early stages of the disease, continues to be poor because of metastasis. In some cases, the cancer is much advanced at the time of diagnosis, further limiting treatment options and effectiveness 20,23 .…”

Section: Practice Implicationsmentioning

confidence: 99%

Coriolus Versicolor Extracts: Relevance in Cancer Management

Szeto¹

2008

Current Oncology

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“…Tumor vaccines may have an adjuvant role in surgically resectable and unresectable NSCLC by consolidating responses to the conventional therapy. Presently, there is no standardized method for preparing vaccines and many questions concerning the optimal source and type of antigens as well as maturation state and activity of dendritic cells are still unsolved [5][6][7][8]. Therefore, the aim of our study was to investigate the influence of autologous tumor cell lysate on the phenotype of dendritic cells generated from peripheral blood of NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Phenotype of dendritic cells generated in the presence of non-small cell lung cancer antigens - preliminary report.

Jankowska

Krawczyk²,

Wojas‐Krawczyk³

et al. 2009

Folia Histochem Cytobiol.

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Therapeutic outcomes of definitively treated non-small-cell lung cancer (NSCLC) are unacceptably poor. It has been proposed that the manipulation of dendritic cells (DCs) as a "natural" vaccine adjuvant may prove to be a particularly effective way to stimulate antitumor immunity. Presently, there is no standardized methodology for preparing vaccines and many questions concerning the optimal source and type of antigens as well as maturation state and activity of DCs are still unsolved. The study population comprised of ten patients with histologically confirmed NSCLC (mean age: 67.63 ± 6.15 years). Resected small tumor pieces were placed in tissue culture dishes containing different growth factors in order to obtain pure cancer cells. Seven days after the operation, the PBMC were collected and monocytes were purified by the adherence to culture dishes. Monocytes were cultured in RPMI 1640 medium supplemented with 10% of autologous plasma in the presence of rhIL-4 and rhGM-CSF to generate immature autologous (DCs). TNF-α with or without tumor cells' lysate were added to maturation of DCs. After 7 days of culture, DCs were harvested and the expression of CD1a, CD83, CD80, CD86 and HLA-DR antigens were analyzed by flow cytometry. We discovered higher (p=0.07) percentage of semimature DCs in tumor cell lysate culture in comparison with TNF-α culture (21.22 ± 16.82% versus 11.27 ± 11.64%). The expression of co-stimulatory and maturation markers (CD86, CD83 and HLA-DR) was higher on DCs from the culture with tumor cell lysate compared with TNF-α culture as a control. Specimen of NSCLC's culture prepared in this way could generate differences in DCs phenotype, which may have an influence on the therapeutic and protective antitumor immunity of the vaccine. Our research seems to be the next step in the development of DC-based vaccine. We are going to continue the investigation to start the preparation of a pattern of immunological vaccine against lung cancer.

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Lung Cancer Immunotherapy

Cited by 65 publications

References 55 publications

Specific and Randomly Derived Immunoactive Peptide Mimotopes of Mycobacterial Antigens

Specific and Randomly Derived Immunoactive Peptide Mimotopes of Mycobacterial Antigens

Coriolus Versicolor Extracts: Relevance in Cancer Management

Phenotype of dendritic cells generated in the presence of non-small cell lung cancer antigens - preliminary report.

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