Autolymphocyte therapy. III. Effective adjuvant adoptive cellular therapy with in vivo anti-tumor specificity against murine melanoma and carcinoma using ex-vivo-activated memory T-lymphocytes.

Autolymphocyte therapy (ALT) is adoptive cellular therapy of neoplastic disease based upon ex vivo activation of lymphocytes by either the supernatant derived from a previously prepared one-way mixed lymphocyte culture (MLC) or using low doses of the mitogenic monoclonal antibody OKT3 and a mixture of previously prepared cytokines (T3CS). We have previously demonstrated that nonspecific ex vivo activation of splenocytes from murine tumor-bearing hosts (TBH) using an MLC-supernatant or T3CS without the use of tumor antigen results in the expansion of the CD44+ (memory) T-cell subset. These CD44+ T-cells are the principal mediators of anti-tumor specificity in the ALT-cell population in advanced metastatic murine tumors and are able to protect against tumor challenge in healthy syngeneic mice (HSM).

Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).

Objective: To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both.

Materials And Methods: Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-depleted PBMC obtained before surgery.

Adoptive transfer of ex vivo-activated memory T-cell subsets with cyclophosphamide provides effective tumor-specific chemoimmunotherapy of advanced metastatic murine melanoma and carcinoma.

Autolymphocyte therapy (ALT) is adoptive cellular therapy of neoplastic disease using ex vivo activation of autologous (human) or syngeneic (murine) lymphocytes from tumor-bearing hosts (TBH) by low doses of anti-CD3 monoclonal antibody (MAb) and a mixture of previously prepared autologous cytokines (T3CS). Ex vivo activation by T3CS without tumor antigen results in expansion of CD44+ (memory) T cells. These memory T cells (ALT cells) mediate in vivo anti-tumor specificity and with cyclophosphamide (CY) are capable of curing metastatic disease in murine TBH.

Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human soft-tissue sarcoma targets with potentiation by cis-diamminedichloroplatinum(II).

Autolymphocyte therapy (ALT) is tumor-specific, adoptive cellular therapy of neoplastic disease using nonspecific ex vivo activation of autologous peripheral blood lymphocytes (PBL), which are composed primarily of memory T-cells (ALT-cells) and are active in patients with metastatic renal cell carcinoma and melanoma. Ex vivo pretreatment of tumor target cells with certain chemotherapeutic agents can enhance susceptibility to lysis by antitumor lymphocytes. To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances ex vivo antitumor cytotoxicity of ALT-cells and if this lysis is mediated by T- and/or NK-cells and is human leukocyte antigen (HLA)-restricted, human soft tissue sarcoma (STS) target cells were derived from primary and metastatic surgical specimens and were incubated with and without CDDP.

Newspaper reporting of the medical literature.

Objective: To examine whether the media are providing information to the public about important medical advances in a timely manner and whether the degree of importance is associated with other aspects of newspaper reporting (presence, extent, and prominence).

Design: The authors explored the amount, extent, prominence, and timeliness of newspaper coverage received by New England Journal of Medicine and JAMA articles published in 1988, by searching ten leading U.S.

Adoptive transfer of ex vivo activated memory T-cells with or without cyclophosphamide for advanced metastatic melanoma: results in 36 patients.

Autolymphocyte therapy (ALT) is the infusion of autologous peripheral blood mononuclear cells (PBMC) activated ex vivo by a cytokine-rich supernatant (T3CS) generated from a previous autologous lymphocyte culture using low doses of the anti-CD3 mitogenic monoclonal antibody. The mechanism of action is enhancement of a recall response by CD45RO+ (memory) T-cells (ALT cells) to host tumour without dependence on exogenous interleukin (IL)-2. The existence of anti-tumour-specific T-cells in melanoma patients has been well described, and efforts to utilise them therapeutically have achieved modest tumour response rates.

Adoptively transferred ex vivo activated memory T cells with cyclophosphamide: effective tumor-specific chemoimmunotherapy of advanced metastatic murine melanoma and carcinoma.

Autolymphocyte therapy (ALT) is adoptive cellular therapy of neoplastic disease based upon ex vivo activation of autologous peripheral blood mononuclear cells by either the supernatant derived from a previously prepared one-way mixed lymphocyte culture (MLC) or using low doses of the mitogenic monoclonal antibody anti-CD3 and a mixture of previously prepared autologous cytokines (T3CS). We have previously demonstrated that nonspecific ex vivo activation of splenocytes from murine tumor-bearing hosts (TBH) using an MLC supernatant or T3CS without the use of tumor antigen results in the expansion of the CD44+ (memory) T-cell subset. These memory T cells or autolymphocytes (ALT cells) mediate in vivo specificity when infused into murine TBH.

Autolymphocyte therapy. II. Dependence of in vivo anti-tumor specificity and long-term immunity against murine melanoma and carcinoma on ex vivo activated donor memory T-cells.

Autolymphocyte therapy (ALT) is tumor-specific adoptive cellular therapy of neoplastic disease in human tumor-bearing hosts based upon nonspecific ex vivo activation of autologous peripheral blood lymphocytes. We have previously demonstrated that nonspecific ex vivo activation of splenocytes from murine tumor-bearing hosts using a mixed-lymphocyte culture supernatant without tumor antigen results in the expansion of the CD44+ (memory) T-cell subset and that depletion of these CD44+ T-cells results in the abrogation of all in vivo anti-tumor effects. To examine other means of generating anti-tumor-specific effectors, splenocytes of C57BL/6J healthy syngeneic mice and mice with B16 melanoma (B16 mice) or Lewis lung (3LL) carcinoma (3LL mice) were activated ex vivo using low doses of the mitogenic monoclonal antibody OKT3 and a mixture of previously prepared autologous cytokines (T3CS).

Autolymphocyte therapy--I. In vivo tumour-specific adoptive cellular therapy of murine melanoma and carcinoma using ex vivo activated memory T-lymphocytes.

Autolymphocyte therapy (ALT) is tumour-specific adoptive cellular therapy of neoplastic disease based upon non-specific ex vivo activation of autologous peripheral blood lymphocytes (PBL), using the supernatant derived from a previously prepared one-way mixed lymphocyte culture (MLC). To determine the requirement for tumour antigen during the activation process, splenocytes from C57BL/6J healthy syngeneic mice (HSM) and tumour-bearing mice (TBM) were activated ex vivo using a MLC-supernatant (MLCS). Ex vivo activation was performed both in the presence (HSM splenocytes) and absence (TBM splenocytes) of a 3M KC1 syngeneic tumour-antigen (STA) extract prepared from Lewis lung (3LL) carcinoma, B16 melanoma, or normal lung.

Adoptive chemoimmunotherapy using ex vivo activated memory T-cells and cyclophosphamide: tumor lysis syndrome of a metastatic soft tissue sarcoma.

Adoptively transferred immune cells in combination with chemotherapeutic agents form the basis for adoptive chemoimmunotherapy (ACIT) of neoplastic disease. Autolymphocytes (ALT-cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor-bearing hosts (TBH) that consist primarily of tumor-specific CD45RO+ (memory) T-cells. These ALT-cells combined with cimetidine (CIM) as autolymphocyte therapy (ALT), have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC).

Adoptive chemoimmunotherapy for the treatment of relapsed and refractory solid tumors using ex vivo activated memory T cells (autolymphocyte therapy) and cyclophosphamide.

Autolymphocytes (ALT cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor-bearing hosts (TBH) that consist primarily of tumor specific CD45RO+ (memory) T cells. These ALT cells combined with cimetidine as autolymphocyte therapy (ALT) have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC). To determine activity of ALT in human TBH with therapy-resistant solid tumors other than RCC and whether it was feasible to combine ALT with chemotherapy, we studied 21 patients with relapsed or primary refractory solid tumors following a study protocol of adoptive chemoimmunotherapy (ACIT) using ALT and cyclophosphamide.

Adoptive immunotherapy of hormone-refractory, stage D2 prostate cancer using ex vivo activated autologous T cells (autolymphocyte therapy): results from a pilot study.

There is no effective therapy available for stage D2 prostate cancer once patients become refractory to hormonal therapy. In a pilot study, we treated 17 patients with hormone-refractory stage D2 prostate cancer using autolymphocyte therapy, an outpatient form of adoptive immunotherapy in which patients are treated with autologous T cells that have been activated ex vivo. Feasibility and safety were documented.

The rapid diagnosis of infectious mononucleosis using an ELISA that detects IgM antibody to a peptide component of Epstein-Barr virus nuclear antigen.

An enzyme-linked immunosorbent assay (ELISA) that detects IgM antibody to a peptide component of the Epstein-Barr virus (EBV) nuclear antigen (EBNA-1) was compared with a conventional rapid heterophil antibody method for the rapid diagnosis of infectious mononucleosis. Discrepancies between the two methods were further analyzed using an indirect immunofluorescence assay to detect antibodies to EBV antigens. We evaluated 298 cases of suspected infectious mononucleosis.

Acute phase reactants and suppressive E-receptor factor in various groups of patients receiving autolymphocyte therapy.

The levels of selected acute phase proteins (APP) and of tumor-associated suppressive E-receptor factor (SER) were determined in sequential serum specimens from (1) cancer patients under treatment with autolymphocyte therapy (ALT) or plasmapheresis, (2) patients with acute infections, (3) patients with autoimmune disorders, and (4) other nonmalignant diseases. The absolute serum levels of APP, including SER, and their patterns of change over time are shown to differ significantly between cancer and non-cancer patients. The absolute levels of APP and the patterns of change over time appear to be useful indicators of immune status and predictors of antitumor response to autolymphocyte (and possibly other anti-cancer) therapy.

Problems in the investigational study and clinical use of cancer immunotherapy.

The last decade has witnessed a veritable explosion in the investigational study and clinical use of immunotherapy for the treatment of cancer. Although this is an exciting development, the promise of cancer immunotherapy has not yet been fulfilled. Why is there an apparent discrepancy between the theory of cancer immunotherapy and the actual results from clinical studies? Michael Osband and Susan Ross suggest that there are several basic problems with the clinical study and therapeutic use of immunotherapy that must be overcome before it can be considered a viable treatment for a broad range of tumors.

Treatment of metastatic renal cell carcinoma with autolymphocyte therapy. Low toxicity outpatient approach to adoptive immunotherapy without use of in vivo interleukin-2.

Thirty-six patients with Stage IV renal cell carcinoma were treated with autolymphocyte therapy (ALT). This new form of adoptive immunotherapy is based on the infusion of relatively small numbers of autologous lymphocytes that are depleted of suppressor cells and immunized in vitro by a method designed for antigen-specific activation using a 3M KCl extract of autologous tumor and an autologous lymphokine mixture. Patients received six monthly infusions of immunized lymphocytes, all on an outpatient basis.

Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma.

To assess the value of autolymphocyte therapy (ALT) in the treatment of metastatic renal-cell carcinoma, 90 patients were randomised to receive every month for six months oral cimetidine plus an infusion of autologous peripheral blood lymphocytes activated in vitro by a previously generated autologous lymphokine mixture, or cimetidine alone. The median follow-up was 15 months. Survival time for the autolymphocyte group was approximately 2.