Targeting TREM2 on tumor-associated macrophages enhances immunotherapy.

Converting checkpoint inhibitor (CPI)-resistant individuals to being responsive requires identifying suppressive mechanisms. We identify TREM2 tumor-associated macrophages (TAMs) as being correlated with exhausted CD8 tumor-infiltrating lymphocytes (TILs) in mouse syngeneic tumor models and human solid tumors of multiple histological types. Fc domain-enhanced anti-TREM2 monoclonal antibody (mAb) therapy promotes anti-tumor immunity by elimination and modulation of TAM populations, which leads to enhanced CD8 TIL infiltration and effector function.

Tuning the Tumor Myeloid Microenvironment to Fight Cancer.

The tumor microenvironment (TME) of diverse cancer types is often characterized by high levels of infiltrating myeloid cells including monocytes, macrophages, dendritic cells, and granulocytes. These cells perform a variety of functions in the TME, varying from immune suppressive to immune stimulatory roles. In this review, we summarize the different myeloid cell populations in the TME and the intratumoral myeloid targeting approaches that are being clinically investigated, and discuss strategies that identify new myeloid subpopulations within the TME.

A phase I study of the antibody drug conjugate ASG-5ME, an SLC44A4-targeting antibody carrying auristatin E, in metastatic castration-resistant prostate cancer.

Background Antibody drug conjugates (ADC) offer the potential of maximizing efficacy while minimizing systemic toxicity. ASG-5ME, an SLC44A4-targeting antibody carrying monomethyl auristatin E (MMAE), a microtubule-disrupting agent, was investigated in men with metastatic castration resistant prostate cancer. Methods The primary objective of this phase I study was to determine maximum tolerated dose (MTD) and recommended phase II dose.

Phase I Trials of Anti-ENPP3 Antibody-Drug Conjugates in Advanced Refractory Renal Cell Carcinomas.

To determine the safety, pharmacokinetics, and recommended phase II dose of an antibody-drug conjugate (ADC) targeting ectonucleotide phosphodiesterases-pyrophosphatase 3 (ENPP3) conjugated to monomethyl auristatin F (MMAF) in subjects with advanced metastatic renal cell carcinoma (mRCC). Two phase I studies were conducted sequentially with 2 ADCs considered equivalent, hybridoma-derived AGS-16M8F and Chinese hamster ovary-derived AGS-16C3F. AGS-16M8F was administered intravenously every 3 weeks at 5 dose levels ranging from 0.

Quality of life analyses in a clinical trial of DPPE (tesmilifene) plus doxorubicin versus doxorubicin in patients with advanced or metastatic breast cancer: NCIC CTG Trial MA.19.

Background: DPPE (tesmilifene) plus doxorubicin (DOX) demonstrated a significant improvement in survival versus DOX in a phase III clinical trial in advanced breast cancer. However, DPPE is associated with unusual toxicity in the form of hallucinations, nausea and vomiting which were anticipated to impact on short-term quality of life (QOL).

Methods: Standard National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) approaches were applied as the primary method to analyze the QOL data from this trial.

Compliance and outcome of patients with stage 1 non-seminomatous germ cell tumors (NSGCT) managed with surveillance programs in seven Canadian centres.

Objective: We evaluate the impact of surveillance programs on the outcome of men with clinical stage 1 NSGCT following orchidectomy.

Patients And Methods: A retrospective review of 197 patients with a minimum of 2 years follow-up at seven cancer centres was conducted. Histological characteristics of the primary tumor were recorded for each patient.

Family caregiver burden: results of a longitudinal study of breast cancer patients and their principal caregivers.

Background: The vital role played by family caregivers in supporting dying cancer patients is well recognized, but the burden and economic impact on caregivers is poorly understood. We prospectively examined the psychosocial, occupational and economic impact of caring for a person with a terminal illness.

Methods: We studied 89 caregivers of women with advanced breast cancer receiving care at either the Ottawa or Hamilton regional cancer centres in Ontario.

Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer.

Objective: To define the optimal treatment for women with stage III or locally advanced breast cancer (LABC).

Evidence: Systematic review of English-language literature retrieved from MEDLINE (1984 to June 2002) and CANCERLIT (1983 to June 2002). A nonsystematic review of the literature was continued through December 2003.

Phase III study of N,N-diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine (BMS-217380-01) combined with doxorubicin versus doxorubicin alone in metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19.

Purpose: N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE; tesmilifene) is a novel agent that augments chemotherapy cytotoxicity in vitro and in vivo. A phase II trial combining DPPE and doxorubicin (DOX) in metastatic breast carcinoma showed increased response over that expected with DOX. We report a phase III trial comparing DOX with DPPE plus DOX in metastatic or recurrent breast cancer.

The Initial Health Assessment: an intervention to identify the supportive care needs of cancer patients.

Background: The first step in effective supportive care delivery is an assessment of patient needs. The Initial Health Assessment Form (IHA) was developed to aid clinicians in recognition and documentation of a patient's supportive care needs during their first visit to a comprehensive cancer centre. The purpose of this study was to determine the relative effectiveness of this instrument as compared to routine practice.

Helping patients make informed choices: a randomized trial of a decision aid for adjuvant chemotherapy in lymph node-negative breast cancer.

Background: In recent years, patients have indicated a desire for more information about their disease and to be involved in making decisions about their care. We developed an aid called the "Decision Board" to help clinicians inform patients with lymph node-negative breast cancer of the risks and benefits of adjuvant chemotherapy. We determined whether adding the Decision Board to the medical consultation improved patient knowledge and satisfaction compared with the medical consultation alone.

A randomized phase II and pharmacokinetic study of the antisense oligonucleotides ISIS 3521 and ISIS 5132 in patients with hormone-refractory prostate cancer.

Purpose: Protein kinase C (PKC)-alpha and Raf-1 are important elements of proliferative signal transduction pathways in both normal and malignant cells. Abrogation of either Raf-1 or PKC-alpha function can both inhibit cellular proliferation and induce apoptosis in several experimental cancer models including prostate cancer cell lines. ISIS 3521 and ISIS 5132 are antisense phosphorothioate oligonucleotides that inhibit PKC-alpha and Raf-1 expression, respectively, and induce a broad spectrum of antiproliferative and antitumor effects in several human tumor cell lines.

The challenge of developing a regional palliative care data system: a tale of two cities.

This article reviews the purposes of health care databases and the findings from a literature review of the use of patient databases in palliative care. We present the history and goals of databases developed in two Canadian settings, Hamilton and Halifax. We present data on the strengths, limitations, and difficulties encountered in each setting.

The multidimensional pain inventory profiles in patients with chronic cancer-related pain: an examination of generalizability.

This study examined the generalizability of the non-malignant pain patient profiles based on the Multidimensional Pain Inventory (MPI) to patients with cancer-related pain. Data were collected from 112 cancer patients. In total, 107/112 patients completed the MPI.