Effective Treatment of Transmissible Venereal Tumors in Dogs with Vincristine and IL2.

Aim: To improve treatment of inoperable transmissible venereal tumors (TVTs) in dogs. Recently, we showed that TVT is sensitive to intratumoral treatment with interleukin-2 (IL2). In addition it is known that TVT is sensitive to intravenous treatment with vincristine.

Treatment of transmissible venereal tumors in dogs with intratumoral interleukin-2 (IL-2). A pilot study.

Aim: To improve the treatment of transmissible venereal tumors (TVTs) in dogs with intratumoral injections of interleukin-2 (IL-2).

Patients And Methods: We treated 13 dogs with 18 natural TVTs with IL-2. The tumors were treated with intratumoral application of 2×10(6) units IL-2.

Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer.

Prophylactic vaccination is arguably the most effective medical preventative method. After local inoculation, vaccines induce antigen-specific systemic immunity, protecting the whole body. Systemic antitumour immunity can cure advanced cancer, but will therapeutic vaccination suffice? A vaccine for castration-refractory prostate cancer (CRPC) was approved by regulatory authority, but its evidence is disputed.

Therapeutic response of untreatable hepatocellular carcinoma after application of the immune modulators IL-2, BCG and melatonin.

Aim: Application of immunotherapy to a patient with untreatable hepatocellular carcinoma.

Case Report: The patient had a tumor of 60 mm in the liver. The pathological anatomic diagnosis was adenoma.

Role of marker lesion when applying intravesical instillations of IL-2 for non-muscle-invasive bladder cancer comparison of the therapeutic effects in two pilot studies.

Aim: Comparison of the therapeutic effect of treatment of non-muscle invasive bladder carcinoma (NMIBC) after intravesical Interleukin-2 (IL-2) instillations in the presence and absence of a marker tumour.

Materials And Methods: Two pilot studies were performed in patients with NMIBC. The first study (10 patients) was performed in Krakow (Poland), the second (26 patients) in Vilnius (Lithuania).

Prognostic significance of peripheral blood CD8highCD57+ lymphocytes in bladder carcinoma patients after intravesical IL-2.

Background: The objective of this study was to evaluate the recurrence-preventing effect of intravesical instillations of interleukin-2 (IL-2) in patients with non-muscle-invasive bladder carcinoma. In addition, this study aimed to determine the significance of immune parameters for recurrence-free interval.

Patients And Methods: Twenty-six patients with non-muscle-invasive bladder carcinoma were treated with intravesical instillations of IL-2 (Proleukin®, Novartis, formerly Chiron) in doses of 9 × 10(6) IU on 5 consecutive days, beginning on the second day after transurethral resection (TUR) of tumours.

Prediction of response in cancer immunotherapy.

This review focuses on the relationship between pre-treatment immune parameter values and outcome of immunotherapy of cancer patients. The evidence presented in this review suggests that there is a relationship between pre-treatment immune parameter values and survival of cancer patients treated with immunotherapy. Tumour-infiltrating immune cells may have a predictive value for immunotherapy, but predictive power might be obtained from peripheral blood leukocytes.

Peripheral blood CD8highCD57+ lymphocyte levels may predict outcome in melanoma patients treated with adjuvant interferon-alpha.

Background: The objective of this study was to evaluate the significance of CD8highCD57+ lymphocytes for the survival of high risk melanoma patients treated with adjuvant interferon-alpha (IFN-alpha).

Patients And Methods: The prognostic significance of peripheral blood CD8highCD57+ lymphocyte levels for survival was analysed retrospectively in 16 IFN-alpha-treated melanoma patients with resected regional lymph node metastases. The survival of the patients was analyzed using the Kaplan-Meier method.

Local therapy of cancer with free IL-2.

This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses.

In vitro and in vivo protein delivery from in situ forming poly(ethylene glycol)-poly(lactide) hydrogels.

Previous studies have shown that stereocomplexed hydrogels are rapidly formed in situ by mixing aqueous solutions of eight-arm poly(ethylene glycol)-poly(L-lactide) and poly(ethylene glycol)-poly(D-lactide) star block copolymers (denoted as PEG-(PLLA)(8) and PEG-(PDLA)(8), respectively). In this study, in vitro and in vivo protein release from stereocomplexed hydrogels was investigated. These hydrogels were fully degradable under physiological conditions.

Changes in cytokine profile during local IL-2 therapy in cancer patients.

Background: Exogenous interleukin 2 (IL-2) can influence the complex cytokine network in vivo. This study investigated the cytokine profile of patients with different malignancies before and after local IL-2 administration.

Patients And Methods: The human TH1 / TH2 cytometric bead array (CBA) kit was used to investigate IL-2, IFNgamma, TNFalpha, IL-4, IL-5 and IL-10 in a control group and in 13 patients.

Locoregional IL-2 low dose applications for gastrointestinal tumors.

Aim: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application.

Methods: Sixteen patients with stages III and IV of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with locoregionally applied IL-2 in low doses.

A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample.

Background: Presently available flow cytometric methods of bromodeoxyuridine (BrdUrd) labelling do not provide information on the cell cycle time (TC) and the growth fraction (GF). In this paper, we describe a novel and simple method to estimate TC and GF from flow cytometric analysis of a single tumour sample after BrdUrd labelling.

Methods: The proposed method is based on two assumptions: (1) the number of labelled cells traversing the cell cycle per unit time is constant and (2) the total number of labelled cells is constant throughout the cycle, provided that cells produced after division are excluded.

Local interleukin-2 and interleukin-12 therapy of bovine ocular squamous cell carcinomas.

Interleukin-2 and interleukin-12 have been used independently to successfully treat the induced and the spontaneous tumours in animals. This trial was done to determine if a combination of IL-2 and IL-12 in the treatment of spontaneous bovine ocular squamous cell carcinomas (BOSCC) would be more successful than IL-2 or IL-12 therapy by themselves. For this trial, we selected 25 BOSCC tumours seen on Holstein Fresian cows in Beatrice, Zimbabwe.

Local interleukin 2 therapy is most effective against cancer when injected intratumourally.

Local interleukin 2 (IL-2) therapy is more effective against systemic tumours than systemic IL-2 therapy, but it remains unclear whether IL-2 should be injected intratumourally or peritumourally. To investigate this question, we treated DBA/2 mice bearing a large subcutaneous syngeneic SL2 lymphoma with either intra or peritumoural IL-2 therapy. Both applications enhanced survival, but intratumourally injected IL-2 was more effective than peritumourally injected IL-2.

Treatment of stage III-IV nasopharyngeal carcinomas by external beam irradiation and local low doses of IL-2.

The therapeutic effect of intratumoural application of Interleukin-2 (IL-2) was studied in patients with stage III-IV nasopharyngeal carcinoma (NPC) that received radiotherapy. Patients with stage III-IV NPC receiving a standard treatment of 7,000 cGy external beam irradiation have a mean disease-free survival of about 1.5 years.

Treatment with IL-2 and IL-12 inhibits tumour cell division in SL2 lymphoma.

We examined which mechanism plays a dominant role in the rejection of solid SL2 lymphoma treated with locally applied IL-2 and/or IL-12. This treatment resulted in about 80% cures. There was a moderate influx of leukocytes in the tissue surrounding tumours; yet these cells failed to invade the solid tumours.

In situ crosslinked biodegradable hydrogels loaded with IL-2 are effective tools for local IL-2 therapy.

We investigated the therapeutic efficacy of recombinant human interleukin-2 (rhIL-2)-loaded, in situ gelling, physically crosslinked dextran hydrogels, locally applied to SL2 lymphoma in mice. The physical crosslinking was established by stereocomplex formation between d-lactic acid oligomers and l-lactic acid oligomers grafted separately to dextrans. The stereocomplex hydrogel as described in our manuscript has several favourable characteristics, which enables its use as system for the controlled release of pharmaceutically active proteins.

Further development of local IL-2 therapy of cancer: multiple versus single IL-2 treatment of transplanted murine colon carcinoma.

We have compared the effect of one and up to four local IL-2 treatments of transplanted MC38 colon carcinoma. A single IL-2 treatment prolonged the survival time ( p=0.015), but no cure was obtained.

Presence of cytotoxic B220+CD3+CD4-CD8- cells correlates with the therapeutic efficacy of lymphoma treatment with IL-2 and/or IL-12.

Cancer treatment with IL-2 and IL-12 is thought to work via enhancement of proliferation and activity of T cells and NK cells. Incubation of cytotoxic T lymphocytes (CTLs) and NK cells with IL-2 and/or IL-12 results in propagation of a distinct cell type called lymphokine-activated killers (LAK) characterized by increased lytic activity against many tumor types. Here we address the question whether cytokine therapy may be efficient in treatment of a LAK-insensitive tumor and, if so, which cell type, other than classic LAK cells, is responsible for tumor cell killing.

Therapeutic effect of a single peritumoural dose of IL-2 on transplanted murine breast cancer.

Interleukin-2 therapy is not clearly effective against breast cancer both in mouse models and in human patients. However, the study of IL-2 therapy of breast cancer remains important, as 3,700 women died from this malignancy in the Netherlands in 2000. Previously we have shown the therapeutical efficacy of a single peritumoural IL-2 application in different experimental models and in veterinary patients.

Mechanisms of macrophage cytotoxicity in IL-2 and IL-12 mediated tumour regression.

IL-2 and IL-12 are promising anti-tumour agents. However, little attention has been paid to the role of macrophages during IL-2/IL-12 mediated tumour rejection. We studied the role of macrophages during IL-2/IL-12 mediated tumour rejection in DBA/2 mice bearing syngeneic SL2 lymphoma.

Predictive value of CD8highCD57+ lymphocyte subset in interferon therapy of patients with renal cell carcinoma.

Background: The aim of this retrospective study was to evaluate the significance of pre-treatment levels of peripheral blood lymphocyte subsets for survival of renal cell carcinoma (RCC) patients treated with interferon-a2b (IFN).

Patients And Methods: CD3+, CD19+, CD16&56+, CD4+, CD8+, CD4+CD45ROhigh and CD8highCD57+ lymphocyte subsets in peripheral blood of 85 advanced RCC patients were determined using flow cytometry. The survival of IFN-treated and non-treated patients was analyzed by gradually testing different cut-off levels of each lymphocyte subset.