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At least 109 records · Page 6Linked to original sources
PubMed2002

Seventeen cases of alopecia areata: combination of SADBE topical immunotherapy with other therapies.

Topical immunotherapy is effective for severe alopecia areata. However, there are patients with alopecia areata refractory to topical immunotherapy alone. We tried SADBE (squaric acid dibutylester) topical immunotherapy combined with topical dry ice cryotherapy, carpronium chloride (a parasympathetic nerve stimulant) and/or oral cepharanthin (a biscoclaur alkaloid) in alopecia areata refractory to topical SADBE. Seventeen patients with alopecia areata (3 multiple, 3 ophiasis, 5 totalis and 6 universalis) were treated with SADBE in our department in 1999 to 2001. In 3 cases (2 multiple and 1 universalis) out of the 17 cases, cosmetically acceptable regrowth of hair was observed in several months with topical SADBE alone. In the other 14 cases, the SADBE therapy alone for several months (mean: 6.9 months) resulted in no or poor regrowth of hair. However, with subsequent combination therapy of topical SADBE for several months (mean: 7.6 months), satisfactory regrowth of hair was observed in 6 of the 14 cases. Our cases indicate that combination therapy of topical SADBE with other therapies can be a choice for alopecia areata which is refractory to topical SADBE therapy alone.

Adjuvants, Immunologic↗
PubMed1976

Bacillus Calmette-Guérin immunotherapy in combination with DTIC (NSC-45388) for the treatment of malignant melanoma.

Combination studies of immunotherapy and DTIC chemotherapy for patients with malignant melanoma are described. At our institute the combination of bacillus Calmette-Guérin (BCG) with DTIC, or DTIC plus methyl-CCNU, has resulted in augmentation of remissions in areas regional to BCG immunization, prolongation of chemotherapy-induced remissions, and significant prolongation of survival compared to the use of DTIC chemotherapy without immunotherapy. Data from other centers have shown that augmentation of remissions for melanoma patients occurred when BCG was combined with DTIC, vincristine, and allogeneic tumor cells. Finally, another study has shown that DTIC combined with BCG has prolonged the disease-free interval and survival in melanoma patients with regional lymph node metastases. The potential inhibition of DTIC metabolism by BCG or Corynebacterium parvum is discussed.

BCG Vaccine↗
PubMed1992

Factors influencing the response and survival of patients with liver metastases from breast cancer receiving OK-432-combined adoptive immunotherapy.

The response and survival of 26 patients with liver metastases from breast cancer, who received OK-432-combined adoptive immunotherapy from 1984 to 1990, were evaluated. OK-432-combined adoptive immunotherapy was comprised sequential treatment via the hepatic artery with a streptococcal preparation, OK-432 (1-5 KE), and adoptive transfer of lymphocytes expanded in T-cell growth factor and sonicated tumor extract antigen. Seventeen (65%) patients responded to the therapy. The median survival time of all patients after treatment was 13 months (range, 2-63 months). Of the 20 prognostic factors analyzed, performance status (PS) alone was related to response (P less than 0.01). The response rate of the patients with a PS of 0-2 was 83% but only 25% in those with a PS of 3 or 4. In univariate analysis, 11 factors significantly influenced the survival: tumor response; size of primary tumor; menopausal status; PS; serum bilirubin, albumin, lactate dehydrogenase and glutamate-oxalate transaminase (aspartate aminotransferase); the extent of liver involvement; and the number and the proliferation rate of transferred lymphocytes. The MST was 22.8 months for the responders versus 2.8 months for the nonresponders (P less than 0.01). In multivariate analysis, the most important factor associated with survival was the tumor response, as well as PS, liver involvement, lactate dehydrogenase and albumin. These results suggest that OK-432-combined adoptive immunotherapy can be considered a candidate for a randomised control study and these factors should be used for stratification.

Breast Neoplasms↗
PubMed2003

Complete regression of experimental solid tumors by combination LEC/chTNT-3 immunotherapy and CD25(+) T-cell depletion.

LEC/chTNT-3, a chemokine fusion protein generated previously in our laboratory, produces a 40-60% reduction in well-established solid tumors of the BALB/c mouse. In this study, CD25(+) T-cell depletion was used in combination with LEC/chTNT-3 treatment to enhance the therapeutic value of this approach. In two tumor models (Colon 26 and RENCA), this combination immunotherapy produced complete regression of established s.c. tumors after 5 consecutive days of i.v. treatment. To show that targeted LEC is critical to these results, similar combination studies were performed with chTNT-3/cytokine fusion proteins consisting of human interleukin 2, murine IFN-gamma, and murine granulocyte macrophage colony-stimulating factor using identical treatment regimens. These studies showed no significant improvement indicating that combination therapy with anti-CD25(+) antisera requires LEC localization to tumor to produce complete regression. To study the mechanism of this remarkable response, immunotherapeutic studies were repeated in knockout mice and showed that successful treatment with CD25(+) depletion was dependent on the presence of IFN-gamma but not perforin. Other studies using real-time PCR, ex vivo proliferation, and intracellular cytokine staining with lymphocytes from tumor draining lymph nodes, suggested that this combination treatment was associated with increased T-helper 1 cytokine expression, enhanced T-cell activation, and increased IFN-gamma production by T cells. Rechallenge experiments showed that combination LEC/chTNT-3 treatment and CD25(+) depletion produced long-acting memory cells capable of preventing re-engraftment of the same but not different tumor cell lines. These studies suggest that LEC/monoclonal antibody fusion proteins, when used in combination with CD25(+) T-cell depletion, is a viable method of immunotherapy for the treatment of solid tumors.

Animals↗
PubMed2006

Photoimmunotherapy for cancer treatment.

Phototherapy, with its effective dose control and light delivery, has become a promising modality for treating malignant and nonmalignant diseases. Photochemical interaction, specifically photodynamic therapy (PDT), and photothermal interaction have been the primary mechanisms for direct cell destruction in the treatment of cancers. Preclinical studies demonstrate that, in addition to direct local cytotoxicity, PDT can also induce systemic immune responses, which may enhance therapeutic effects on primary tumors and on metastases at distant sites. Selective photothermal therapy, using an in situ application of light-absorbing dye, has also proven to be an effective method for local treatment of tumors. When combined with immunotherapy, the effects of phototherapy can be amplified, potentially making the photoimmunotherapy a systemic treatment modality. This phototherapy-immunotherapy combination, particularly in conjunction with immunoadjuvant, has been used in preclinical studies. The efficacy and long-term effects of such a combination are summarized and the recent experimental results are presented. A new immunoadjuvant, glycated chitosan (GC), has been used to enhance photochemical and photothermal therapies. The PDT-GC combination in the treatment of mammary tumors and lung tumors in mice provided significant improvement in the long-term survival of tumor-bearing animals. The use of GC in dye-assisted laser photothermal therapy also provided long-term curative effects and antitumor immune responses in the treatment of metastatic tumors in rats. The immune responses induced by phototherapy and enhanced by immunotherapy could become important mechanism in the control of metastatic tumors.

Adjuvants, Immunologic↗
PubMed1994

An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis.

BACKGROUND/AIMS: Immunotherapy using interleukin 2 has had disappointing results in the treatment of colon cancer. Overcoming escape mechanisms, such as lack of antigen presentation and absence of accessory adhesion molecules on cancer cells, may increase its efficiency. We tried to do so by modifying the phenotype of the weakly immunogenic rat colon cancer PROb cells with sodium butyrate. METHODS: After in vitro treatment with butyrate, PROb cells were tested for lymphokine-activated killer cell sensitivity and, using cytofluorometry, expression of adhesion molecules. We then treated established PROb peritoneal carcinomatoses with intraperitoneal injections of interleukin 2 and butyrate. Tumors were studied histologically and immunohistochemically. We tested the specificity of the immune protection by subsequent subcutaneous challenges with either PROb or glioma cells and by Winn's assay. RESULTS: Butyrate increased lymphokine-activated killer cell sensitivity and expression of major histocompatibility complex class I and intercellular adhesion molecule 1 in vitro. Interleukin 2/butyrate combination resulted in cases of complete cure of carcinomatosis with specific protection against PROb cells. We noticed a complex stroma reaction with numerous functional antigen presenting cells close to PROb cells. CONCLUSIONS: The complete regression of tumor masses may be attributed, at least in part, to a butyrate-induced increase in immunogenicity of the cancer cells. This new combined immunotherapy may be of interest in the treatment of colon cancer.

Adenocarcinoma↗
PubMed1986

Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo: survival benefit and mechanisms of tumor escape in mice undergoing immunotherapy.

The studies described in this paper showed that the combination of i.v.-transferred lymphokine-activated killer (LAK) cells and i.p. injections of recombinant interleukin-2 (RIL-2) was highly effective in vivo in reducing established pulmonary metastases of natural killer cell-resistant, MCA-105 sarcoma and B16 melanoma in mice. A 3-day in vitro incubation of normal C57BL/6 splenocytes in medium containing pure RIL-2 generated LAK cells that, when combined with RIL-2, reduced the mean number of established pulmonary micrometastases of the B16 melanoma and of the MCA-105 sarcoma from 179 and 140, respectively (in groups treated with Hanks' balanced salt solution alone), to 12 (P = 0.01) and 6 (P = 0.01), respectively. This combined immunotherapy also consistently resulted in significant prolongation of survival in mice with established, 3-day or 10-day pulmonary metastases of the MCA-105 sarcoma. Mice autopsied at time of death revealed a massive involvement of tumor in the lungs and liver in the group receiving Hanks' balanced salt solution alone compared to a small number of residual large lung or liver metastases in the group receiving LAK cells plus RIL-2. Experiments were designed to test whether variants existed in the original tumor cell inoculum that were resistant to killing by LAK cells and thus could account for the metastases that "escaped" the combined immunotherapy of LAK cells plus RIL-2 in vivo. Metastases of the MCA-105 sarcoma that escaped the combined therapy of LAK cells plus RIL-2 were dissected from the organs of mice upon autopsy and directly tested for susceptibility in vitro to lysis by LAK cells in 4-h and 18-h 51Cr release assays. Target cells derived from the metastases were lysed to an equivalent extent as those prepared from a fresh MCA-105 sarcoma that was growing s.c. In addition, successful reduction of pulmonary metastases established by the i.v. infusion of MCA-105 sarcoma cells obtained from metastases that escaped a prior round of therapy with LAK cells and RIL-2 could be achieved in vivo by the combined immunotherapy as well as by high doses of RIL-2 alone. Culture adapted, natural killer cell-resistant B16 melanoma cells surviving two successive treatments with LAK cells in vitro remained as susceptible to LAK cell lysis as untreated B16 melanoma cells in 18-h 51Cr release assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

OK-432-combined adoptive immunotherapy as a prognostic factor in peritoneal metastasis from gastric cancer.

Prognostic factors, such as preoperative status, intraoperative findings, and postoperative treatments, were evaluated in 61 patients with peritoneal metastasis from gastric cancer treated in our facility between 1979 and 1991. Since 1986, 23 patients have been treated with OK-432-combined adoptive immunotherapy (AIT). OK-432-combined AIT is a sequential treatment via a catheter inserted into the abdominal cavity, using a streptococcal preparation, OK-432, followed by the transfer of lymphocytes cultured with T cell growth factor and sonicated tumor extract. A univariate analysis showed that six factors consisting of: (1) age, (2) resection of primary lesion, (3) grade of peritoneal metastasis or serosal invasion, (4) chemotherapy, (5) OK-432, and (6) OK-432-combined AIT influenced survival. The survival of the patients given OK-432-combined AIT (median survival time; MST = 7.5 months) was significantly (P = 0.0267) longer than that of those not receiving OK-432-combined AIT (MST = 4.3 months). A multivariate analysis showed that the most significant factors associated with survival were chemotherapy, resection of the primary lesion, and OK-432-combined AIT. Since these three factors are all therapeutic procedures, the use of combination therapy including OK-432-combined AIT is thus expected to prolong the survival of gastric cancer patients with peritoneal metastasis.

Adult↗
PubMed2003

[Significance of gefitinib combined with immunotherapy in tumor-bearing mice].

Gefitinib (brand name: Iressa) is a drug approved for molecule-targeting therapy in lung carcinoma patients. There are still many unresolved problems concerning the safety and mechanism of action of this drug. Based on the expectation that this drug combined with immunotherapy would be highly effective, we recently conducted an experiment in tumor-bearing mice. In this experiment, however, the tumor was not significantly reduced in size by this combined therapy. However, since the tumor in this animal model was EGFR positive and because tumor growth tended to be suppressed in mice with higher immune activity, it seems likely that additional studies of this therapy will contribute to identifying the optimum drugs to be combined with gefitinib and the optimum method of dosing that will lead to satisfactory efficacy and safety of gefitinib combined with immunotherapy.

Animals↗
PubMed2001

Biological treatment in acute myelogenous leukaemia: how should T-cell targeting immunotherapy be combined with intensive chemotherapy?

T-cell targeting immunotherapy is now considered as a possible strategy in the treatment of acute myelogenous leukaemia (AML). Clinical importance of antileukaemic T-cell reactivity after allogeneic stem cell transplantation (SCT) is well established and the early experience from IL-2 therapy suggests that even autologous T-cells can mediate antileukaemic reactivity. The clinical experience also indicates that immunotherapy should begin when the leukaemia cell burden is minimal, and the detection of an operative cellular immune system, even in patients with chemotherapy-induced cytopenia, further suggests that it is possible to begin T-cell targeting therapy early after chemotherapy while patients are still cytopenic. However, adult patients in particular have a T-cell defect after chemotherapy that may last for several months. For this reason immunotherapy should probably be continued or repeated until a maximal effect is achieved when the patients no longer have a T-cell defect. This treatment approach may also be considered in combination with autologous SCT. T-cell targeting regimens should include, if possible, several therapeutic components. Firstly, native AML blasts can function as accessory cells during T-cell activation and in vivo therapy with T-cell growth factors (e.g., IL-2, IL-15) may then enhance antileukaemic reactivity or non-specific cytotoxicity against the AML cells; and secondly, a further enhancement of AML-specific reactivity may be achieved by vaccination with AML-specific peptides, immunisation with AML-blasts expressing a dendritic cell phenotype, or exposure to normal antigen-presenting cells (APC) pulsed with or expressing AML-specific peptide sequences.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Bone metastasis as a prognostic factor in breast cancer patients with liver metastasis given OK-432-combined adoptive immunotherapy via the hepatic artery.

The outcome in 31 patients with liver metastases from breast cancer given OK-432-combined adoptive immunotherapy via the hepatic artery was analyzed. Patients received intraarterial OK-432, a streptococcal preparation, followed by the transfer of autologous lymphocytes cultured with autologous tumor extract and interleukin-2 for 9-13 days. Liver lesions were evaluable in 11 of the 12 patients with bone metastasis (group A) and in 16 of the 19 patients without bone metastasis (group B). Complete response (CR) in the liver was attained in 8 patients in group A, but in only 1 in group B (p < 0.01). In group A, radiological features of all metastatic foci of bone improved after CR in the liver. Moreover, the median survival time (MST) of group A (20 months) was longer (p = 0.06) than that of group B patients with extra-hepatic metastasis (n = 12; MST = 6 months), while group B patients with liver metastasis alone (n = 7) showed a MST similar to that of group A. Thus, loco-regional immunotherapy via the hepatic artery was found to be useful in controlling both liver and bone metastasis from breast cancer. Moreover, in breast cancer patients with liver metastasis, bone metastasis appears to be a prognostic factor associated with good response to this immunotherapy.

Adult↗
PubMed1999

IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guérin immunotherapy.

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.

Adjuvants, Immunologic↗
PubMed1998

Induction of differentiation in maxillary adenoid cystic carcinomas by adoptive immunotherapy in combination with chemoradiotherapy.

The successful treatment results of a case of maxillary adenoid cystic carcinoma (ACC) and the possibility of differentiation of ACC cells with chemoradioimmunotherapy are described. Combined therapy was applied to two maxillary ACCs. Adoptive immunotherapy consisted of intra-arterial injection of lymphokine-activated killer cells (total 9.0 x 10(8) cells) and recombinant interleukin-2 (1.8 x 10(5) U) and interferon-gamma (1.8 x 10(5) U) was combined with 60Co radiation (50 Gy), 5-fluorouracil (4000 mg) and peplomycin (10 mg). Immunohistochemical staining of the biopsy material obtained during the therapy revealed a marked decrease of proliferating cell nuclear antigen-positive cells and a prominent increase of Lewis Y antigen- and bone morphogenetic protein-2-positive cells. The disappearance of tumour cells and the remodeling of the sinus wall with calcification in the sinus cavity, which had been occupied by the tumour, were observed after therapy in both patients. Adoptive immunotherapy in combination with chemoradiotherapy is useful for the treatment of ACC.

Aged↗
PubMed1993

The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from gastric or colorectal cancers.

Twenty-four patients with liver metastases from gastric or colorectal cancer were treated with OK-432-combined adoptive immunotherapy (AIT). Lymphocytes isolated from regional lymph nodes or peripheral blood were cultured with medium containing T cell growth factor and sonicated tumor extract antigen (SE-Ag) for 9-13 days. The cultured lymphocytes were transferred mainly through the hepatic artery after the administration of OK-432, a streptococcal preparation. Sixteen of the 24 patients received a low dose of anti-cancer agents between the OK-432 injection and cell transfer. When cultured without SE-Ag, regional lymph node lymphocytes (RLNL) showed significantly (P < 0.05) higher cytotoxic activity against autologous tumor cells and, on the contrary, lower cytotoxic activity against K562 than peripheral blood lymphocytes (PBL). When cultured with SE-Ag, cytotoxicity of RLNL against autologous tumor cells was nearly equivalent to that of PBL. The blastogenesis of fresh PBL to SE-Ag was significantly (P < 0.05) augmented after the OK-432-combined AIT. Two patients showed complete response and 4 patients showed partial response among 19 patients who had evaluable lesions. Five patients whose liver metastases were resected were treated with OK-432-combined AIT as an adjuvant therapy. To date they are alive without recurrence in the liver.

Adult↗
PubMed1985

[Clinical value of postoperative chemotherapy for non-small cell lung cancer--with special reference to long-term combined chemotherapy combined with immunotherapy].

The main reason for unfavourable surgical outcome of lung cancer is latent distant metastases over looked during surgery, which ultimately cause recurrence, or death of the patients even in cases undergoing curative surgery. This fact necessitates the indispensable use of systemic adjuvant therapy in patients under going surgery for lung cancer. There have been mary reports concerning the clinical efficacy of surgical adjuvant chemotherapy for non-small cell lung cancer using various kinds of drugs in various treatment modalities, but the results have been controversial. During the past eleven years, we have used postoperative chemotherapy in three ways over three different periods: in the earliest period, short-term combined chemotherapy (STCC) was used, in the middle period, intermittent long-term combined chemotherapy (ILTCC) was used in combination with immunotherapy for a randomized group, and in the latest period, when continuous long-term combined chemotherapy (CLTCC) with immunotherapy was employed. A comparison was then made between these three kinds of treatment groups. In Comparing of the results obtained for the earliest and middle periods, ILTCC showed a significantly improved beneficial effect over STCC in terms of further increased survival rate. Furthermore, by randomized study, it was clarified that the favourable effect of ILTCC was further improved by concomitant use of immunotherapy. CLTCC with immunotherapy carried out in the latest period seemed to be prevent early recurrences in patients with stage I or II who underwent curative surgery, even though a short-term observation period of for 20 months was employed. It is conceivable that the latest treatment modality used will exerted best the most favourable beneficial effect in comparison with the two early treatments. A review of the literature was presented along with a discussion of the clinical value of chemotherapy and immunochemotherapy as a surgical adjuvant.

Adenocarcinoma↗
PubMed1989

Immunotherapy of localized, intermediate, and diffuse forms of American cutaneous leishmaniasis.

The clinical efficacy of immunotherapy for localized American cutaneous leishmaniasis with a combination of heat-killed Leishmania mexicana amazonensis promastigotes and viable BCG (bacille Calmette Guérin) has been compared with meglumine antimoniate chemotherapy and with BCG alone in a controlled clinical study in 217 patients. The results in the first two groups were comparable, with greater than 90% clinical cures with an average time of 16-18 w required for healing. The cure rate was considerably lower (42%) and more prolonged in the group receiving BCG alone. Secondary effects were observed in less than 5% of the patients receiving combined immunotherapy or BCG alone. In contrast, 49% of the patients receiving chemotherapy showed side effects. High therapeutic efficacy was also observed using combined immunotherapy in patients with intermediate and diffuse cutaneous leishmaniasis who were previously unresponsive to chemotherapy. Cure or clinical improvement was seen in all 11 patients with intermediate forms of the disease, and marked clinical improvement was observed in 9 of 10 patients with diffuse disease. The results on the efficacy of the combined vaccine in immunotherapy for American cutaneous leishmaniasis provide a strong rationale for studying its effectiveness in prophylactic trials.

Adolescent↗
PubMed2001

Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.

To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.

Animals↗